Post on 10-Aug-2019
transcript
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-2D
EC
2000
[Aba
ciog
lu(1
994)
]Y.
H.
Aba
ciog
lu,
T.R
.F
outs
,J.
D.
Lam
an,
E.
Cla
asse
n,S
.H
.P
incu
s,J.
P.M
oore
,C
.A
.R
oby,
R.
Kam
in-L
ewis
,&
G.
K.
Lew
is.
Epi
tope
Map
ping
and
Topo
logy
ofB
acul
oviru
s-E
xpre
ssed
HIV
-1gp
160
De-
term
ined
with
aP
anel
ofM
urin
eM
onoc
lona
lAnt
ibod
ies.AID
SR
es
Hu
mR
etr
oviru
ses1
0:37
1–38
1,19
94.
(Med
line:
9434
7461
)N
otes
:Thi
rty
MA
bsw
ere
obta
ined
from
BA
LB/c
mic
eim
mun
ized
with
rgp1
60LA
Iexp
ress
edin
bacu
lovi
rus.
The
sean
tibod
ies
map
to4
dom
ains
:gp1
20C
1,C
2,C
3/V
4,an
dth
ecy
topl
asm
icta
ilof
gp41
.All
epito
pes
wer
eex
pose
don
rgp1
60w
ithou
tde
natu
ring
the
prot
ein,
but
6/8
epito
pes
map
ped
ingp
120
are
not
expo
sed
unle
ssth
epr
otei
nis
dena
ture
d,sh
owin
grg
p160
and
rgp1
20fo
lddi
ffere
ntly
.
[Ace
l(19
98)]
A.A
cel,
B.E
.Uda
shki
n,M
.A.W
ainb
erg,
&E
.A.F
aust
.E
ffi-
cien
tgap
repa
irca
taly
zed
invi
tro
byan
intr
insi
cD
NA
poly
mer
ase
activ
ityof
hum
anim
mun
odefi
cien
cyvi
rus
type
1In
tegr
ase.
JV
irol7
2:20
62–7
1,19
98.
(Med
line:
9813
9101
)N
otes
:Int
rinsi
cpo
lym
eras
eac
tivity
that
can
cata
lyze
gap
repa
irw
asde
scrib
edfo
rH
IVIn
tegr
ase.
Thi
sac
tivity
was
inhi
bite
dby
the
MA
b35
,tha
tbin
dsto
KA
KIIR
DY
GK
atth
eC
-ter
men
dof
Inte
gras
e.
[Ahl
uwal
ia(1
997)
]A
.A
hluw
alia
,K
.G
okul
an,
I.N
ath,
&D
.N
.R
ao.
Mod
-ifi
catio
nof
deliv
ery
syst
emen
hanc
esM
HC
nonr
estr
icte
dim
mun
ogen
icity
ofV
3lo
opre
gion
ofH
IV-1
gp12
0.M
icro
bio
lIm
mu
no
l41:
779–
84,
1997
.(M
edlin
e:98
0657
59).
[Ake
rblo
m(1
990)
]L.
Ake
rblo
m,
J.H
inku
la,
P.-A
.B
rolid
en,
B.
Mak
italo
,T.
Frid
berg
er,
J.R
osen
,M
.V
illac
res-
Erik
sson
,B
.M
orei
n,&
B.
Wah
ren.
Neu
tral
izin
gcr
oss-
reac
tive
and
non-
neut
raliz
ing
mon
oclo
nala
ntib
odie
sto
HIV
-1gp
120.
AID
S4:
953–
960,
1990
.(M
edlin
e:91
0838
89).
[Alla
way
(199
3)]
G.P
.Alla
way
,A.M
.Ryd
er,G
.A.B
eaud
ry,&
P.J.
Mad
den.
Syn
ergi
stic
inhi
bitio
nof
HIV
-1en
velo
pe-m
edia
ted
cell
fusi
onby
CD
4-ba
sed
mol
ecul
esin
com
bina
tion
with
antib
odie
sto
gp12
0or
gp41
.A
IDS
Re
sH
um
Re
trov
iru
ses9
:581
–587
,199
3.(M
edlin
e:93
3787
78).
[Als
mad
i(19
97)]
O.A
lsm
adi,
R.H
erz,
E.M
urph
y,A
.Pin
ter,
&S
.A.T
illey
.Ano
vela
ntib
ody-
depe
nden
tcel
lula
rcyt
otox
icity
epito
pein
gp12
0is
iden
tified
bytw
om
onoc
lona
lant
ibod
ies
isol
ated
from
alo
ng-t
erm
surv
ivor
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
infe
ctio
n.JV
irol7
1:92
5–33
,199
7.(M
edlin
e:97
1510
73).
[Als
mad
i&T
illey
(199
8)]
O.A
lsm
adi&
S.A
.Till
ey.A
ntib
ody-
depe
nden
tcel
-lu
larc
ytot
oxic
itydi
rect
edag
ains
tcel
lsex
pres
sing
hum
anim
mun
odefi
cien
cyvi
rus
type
1E
nvel
ope
ofpr
imar
yor
labo
rato
ry-a
dapt
edst
rain
sby
hum
anan
d
chim
panz
eem
onoc
lona
lant
ibod
ies
ofdi
ffere
ntep
itope
spec
ifici
ties.
JV
irol
72:2
86–9
3,19
98.
(Med
line:
9808
0415
).
[Altm
eyer
(199
9)]
R.A
ltmey
er,E
.Mor
dele
t,M
.Gira
rd,&
C.V
idal
.E
xpre
s-si
onan
dde
tect
ion
ofm
acro
phag
etr
opic
HIV
-1gp
120
inth
ebr
ain
usin
gco
nfor
mat
ion-
depe
nden
tant
ibod
ies.Viro
log
y25
9:31
4–21
,199
9.(M
edlin
e:99
3190
00).
[And
erss
on(1
997)
]A
.Z.E
.And
erss
on,E
.Kra
mbo
vitis
,&C
.A.B
orre
baec
k.In
duct
ion
ofan
tigen
-spe
cific
isot
ype
switc
hing
byin
vitr
oim
mun
izat
ion
ofhu
man
naiv
eB
lym
phoc
ytes
.Imm
un
ol
Me
tho
ds2
00:1
81–1
90,
1997
.(M
edlin
e:97
1585
97)
Not
es:
Atw
o-st
epinvi
tro
imm
uniz
atio
npr
otoc
olis
desc
ribed
,whi
chyi
elds
anis
otyp
esw
itch.
[And
ris(1
992)
]J.
S.
And
ris,
S.
John
son,
S.
Zol
la-P
azne
r,&
J.D
.C
apra
.M
olec
ular
char
acte
rizat
ion
offiv
ean
ti-hu
man
imm
unod
efici
ency
viru
sty
pe1
antib
ody
heav
ych
ains
reve
als
exte
nsiv
eso
mat
icm
utat
ion
typi
cal
ofan
antig
en-d
riven
imm
une
resp
onse
.P
roc
Na
tlA
cad
Sci
US
A88:
7783
–778
8,19
92.
(Med
line:
9135
2074
).
[And
rus
(199
8)]
L.A
ndru
s,A
.M
.P
rince
,I.
Ber
nal,
P.M
cCor
mac
k,D
.H
.Le
e,M
.K.G
orny
,&S
.Zol
la-P
azne
r.P
assi
veim
mun
izat
ion
with
ahu
man
imm
unod
efici
ency
viru
sty
pe1-
neut
raliz
ing
mon
oclo
nal
antib
ody
inH
u-P
BL-
SC
IDm
ice:
isol
atio
nof
ane
utra
lizat
ion
esca
peva
riant
.J
Infe
ctD
is17
7:88
9–97
,199
8.(M
edlin
e:98
1945
83).
[Are
ndru
p(1
995)
]M
.Are
ndru
p,L.
Ake
rblo
m,P
.M.H
eega
ard,
J.O
.Nie
lsen
,&
J.E
.H
anse
n.T
heH
IV-1
V3
dom
ain
onfie
ldis
olat
es:
part
icip
atio
nin
gene
ratio
nof
esca
pevi
rus
invi
voan
dac
cess
ibili
tyto
neut
raliz
ing
antib
odie
s.A
rch
Viro
l140
:655
–670
,19
95.
(Med
line:
9531
4457
)N
otes
:T
hean
ti-V
3A
btit
rein
patie
ntse
rum
was
gene
rally
low
agai
nsta
utol
ogou
svi
rus
isol
ated
late
rth
anth
ese
rum
sam
ple,
inco
ntra
stto
ahi
gher
titre
agai
nst
pept
ides
corr
espo
ndin
gto
viru
sis
olat
edea
rlier
than
the
seru
msa
mpl
e.T
heau
thor
sco
nclu
deth
atth
eV
3do
mai
nis
subj
ect
toim
mun
osel
ectio
nin
vivo
,an
dth
atV
3on
early
field
viru
sis
less
acce
ssib
leto
NA
bsth
anth
eV
3lo
opon
labo
rato
ryst
rain
s.
[Are
ndru
p(1
993)
]M
.A
rend
rup,
A.
Son
nerb
org,
B.
Sve
nner
holm
,L.
Ake
rblo
m,C
.Nie
lsen
,H.C
laus
en,S
.Olo
fsso
n,J.
O.N
iels
en,&
J.E
.S.
Hen
sen.
Neu
tral
izin
gan
tibod
yre
spon
sedu
ring
hum
anim
mun
odefi
cien
cyvi
rus
type
1in
fect
ion:
type
and
grou
psp
ecifi
city
and
vira
lesc
ape.
JG
en
Viro
l74:
855–
863,
1993
.(M
edlin
e:93
2603
99).
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-3D
EC
2000
[Arm
stro
ng&
Dim
moc
k(19
96)]
S.
J.A
rmst
rong
&N
.J.
Dim
moc
k.Va
ry-
ing
tem
pera
ture
-dep
ende
nce
ofpo
st-a
ttach
men
tneu
tral
izat
ion
ofhu
man
im-
mun
odefi
cien
cyvi
rus
type
1by
mon
oclo
nala
ntib
odie
sto
gp12
0:id
entifi
-ca
tion
ofa
very
early
fusi
on-in
depe
nden
teve
ntas
ane
utra
lizat
ion
targ
et.
JG
en
Viro
l77:
1397
–140
2,19
96.
(Med
line:
8757
979)
.
[Arm
stro
ng(1
996)
]S
.J.A
rmst
rong
,T.L
.McI
nern
ey,L
.McL
ain,
B.W
ahre
n,J.
Hin
kula
,M.L
evi,
&N
.J.D
imm
ock.
Two
neut
raliz
atio
nan
ti-V
3m
ono-
clon
alan
tibod
ies
actb
yaf
fect
ing
diffe
rent
func
tions
ofhu
man
imm
unod
efi-
cien
cyvi
rus
type
1.JG
en
Viro
l77:
2931
–294
1,19
96.(
Med
line:
9715
2500
).
[Bab
a(2
000)
]T.
W.B
aba,
V.Li
ska,
R.H
ofm
ann-
Lehm
ann,
J.V
lasa
k,W
.Xu,
S.
Aye
huni
e,L.
A.
Cav
acin
i,M
.R
.P
osne
r,H
.K
atin
ger,
G.
Stie
gler
,B
.J.
Ber
nack
y,T.
A.
Riz
vi,
R.
Sch
mid
t,L.
R.
Hill
,M
.E
.K
eelin
g,Y.
Lu,
J.E
.W
right
,T.
C.
Cho
u,&
R.
M.
Rup
rech
t.H
uman
neut
raliz
ing
mon
oclo
nal
antib
odie
sof
the
IgG
1su
btyp
epr
otec
t.Na
tMe
d6:2
00–6
,200
0.(M
edlin
e:20
1241
78).
[Bac
k(1
993)
]N
.K.T
.Bac
k,L.
Sm
it,M
.Sch
utte
n,P.
L.N
ara,
M.T
ersm
ette
,&
J.G
ouds
mit.
Mut
atio
nsin
Hum
anIm
mun
odefi
cien
cyV
irus
Type
1gp
41A
ffect
Sen
sitiv
ityto
Neu
tral
izat
ion
bygp
120
Ant
ibod
ies.J
Viro
l67:
6897
–69
02,1
993.
(Med
line:
9401
6886
)N
otes
:Thr
eecl
osel
yre
late
dcl
ones
wer
ede
rived
from
ane
utra
lizat
ion
resi
stan
tIIIB
isol
ate
that
had
been
pass
aged
ina
chim
panz
ee.g
p41
mut
atio
nsw
ere
show
nto
prof
ound
lyal
tert
heab
ility
ofV
3lo
opM
Abs
5023
and
178.
1to
neut
raliz
e.C
ritic
alsu
bstit
utio
nsin
gp41
wer
e66
8an
d67
5,cl
ose
toth
eim
mun
ogen
icdo
mai
n66
2-66
8,or
ELD
KW
AS
.Le
sspr
ofou
ndin
hibi
tion
was
obse
rved
for
the
anti-
CD
4bi
ndin
gsi
teM
Ab
GP
13.
[Bag
ley
(199
4)]
J.B
agle
y,P.
J.D
illon
,C.R
osen
,J.R
obin
son,
J.S
odro
ski,
&W
.A.M
aras
co.
Str
uctu
ralC
hara
cter
izat
ion
ofB
road
lyN
eutr
aliz
ing
Hum
anM
onoc
lona
lAnt
ibod
ies
Aga
inst
the
CD
4B
indi
ngS
iteof
HIV
-1gp
120.Mo
lIm
mu
no
l31(
15):1
149–
1160
,199
4.(M
edlin
e:95
0213
25)N
otes
:Thi
spa
per
isa
deta
iled
stud
yof
the
V-D
-Jhe
avy
chai
nus
age
and
V-J
light
chai
nus
age
for
the
thre
em
onoc
lona
lsth
atbi
ndto
the
HIV
-1en
velo
peC
D4
bind
ing
site
:F
105,
15e
and
21h.
Diff
eren
tge
rmlin
ege
nes
wer
eus
ed,
and
ther
ew
asev
iden
cefo
ran
tigen
-driv
ecl
onal
sele
ctio
nof
som
atic
mut
atio
ns.E
ight
posi
tions
inth
ehe
avy
chai
nan
dtw
oin
the
light
chai
nco
mpl
emen
tarit
yde
term
inin
gpo
sitio
nsw
ere
iden
tical
inth
eth
ree
Mab
s.
[Bai
(200
0)]
Y.B
ai,Y
.Zha
o,T.
Yu,M
.P.D
ieric
h,&
Y.H
.Che
n.A
ntib
odie
sto
HIV
-1gp
41re
cogn
ize
synt
hetic
pept
ides
ofhu
man
IFN
-alp
haan
dIF
N-b
eta.
IntA
rch
Alle
rgy
Imm
un
ol12
1:17
0–2,
2000
.(M
edlin
e:20
1711
60).
[Ban
apou
r(1
987)
]B
.Ban
apou
r,K
.Ros
enth
al,L
.Rab
in,V
.Sha
rma,
L.Yo
ung,
J.F
erna
ndez
,E.E
ngle
man
,M.M
cGra
th,G
.Rey
es,&
J.Li
fson
.C
hara
cter
-iz
atio
nan
dE
pito
peM
appi
ngof
aH
uman
Mon
oclo
nalA
ntib
ody
Rea
ctiv
ew
ithth
eE
nvel
ope
Gly
copr
otei
nof
Hum
anIm
mun
odefi
cien
cyV
irus.
JIm
-m
un
ol1
39:4
027–
4033
,198
7.(M
edlin
e:88
0887
54).
[Ban
dres
(199
8)]
J.C
.B
andr
es,
Q.
F.W
ang
QF
,J.
O’L
eary
,F.
Bal
eaux
,A
.A
mar
a,J.
A.
Hox
ie,
&S
.-P.
M.
K.
Gor
ny.
Hum
anim
mun
odefi
cien
cyvi
rus
(HIV
)en
velo
pebi
nds
toC
XC
R4
inde
pend
ently
ofC
D4,
and
bind
-in
gca
nbe
enha
nced
byin
tera
ctio
nw
ithso
lubl
eC
D4
orby
HIV
enve
lope
degl
ycos
ylat
ion.
JV
irol7
2:25
00–2
504,
1998
.(M
edlin
e:98
1391
53).
[Bar
bas
III(1
992)
]C
.F.
Bar
bas
III,
E.
Bjo
rling
,F.
Chi
odi,
N.
Dun
lop,
D.C
abab
a,T.
M.J
ones
,S.L
.Zeb
edee
,M.A
.Per
sson
,P.A
.Nar
a,E
.Nor
-rb
y,&
etal
.R
ecom
bina
nthu
man
Fab
frag
men
tsne
utra
lize
hum
anty
pe1
imm
unod
efici
ency
viru
sin
vitr
o.P
roc
Na
tlA
cad
Sci
US
A89:
9339
–934
3,19
92.
(Med
line:
9302
8460
).
[Bar
bas
III(1
993)
]C
.F.B
arba
sIII
,T.A
.Col
let,
P.R
oben
,J.B
inle
y,W
.Am
-be
rg,D
.Hoe
kstr
a,D
.Cab
ana,
T.M
.Jon
es,R
.A.W
illia
mso
n,G
.R.P
ilkin
g-to
n,N
.L.H
aigw
ood,
A.C
.Sat
tert
hwai
t,I.
San
z,&
D.R
.Bur
ton.
Mol
ecul
arpr
ofile
ofan
antib
ody
resp
onse
toH
IV-1
aspr
obed
byco
mbi
nato
riall
ibra
ries.
JM
olB
iol2
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Viru
sTy
pe1
Inte
gras
eby
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Fab
Fra
gmen
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Spe
cific
Mon
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nal
Ant
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yS
ugge
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that
Diff
eren
tM
ultim
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bits
3‘-
end
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essi
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dtr
ansf
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Thi
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gw
ithm
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min
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afet
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mun
ogen
icity
ofan
HLA
-bas
edH
IVen
velo
pepo
ly-
vale
ntsy
nthe
ticpe
ptid
eim
mun
ogen
.A
IDS
12:1
291–
300,
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e:98
3721
13).
Ant
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yR
efer
ence
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EC
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[Bed
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s(1
999)
]S
.Bed
dow
s,S
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ter,
R.C
hein
gson
g,C
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e-be
r.C
ompa
rison
ofth
ean
tibod
yre
pert
oire
gene
rate
din
heal
thy
volu
ntee
rsfo
llow
ing
imm
uniz
atio
nw
itha
mon
omer
icre
com
bina
ntgp
120
cons
truc
tde
rived
from
aC
CR
5/C
XC
R4-
usin
ghu
man
imm
unod
efici
ency
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sty
pe1
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ate
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d-ne
y,D
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i,K
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d,&
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.V.E
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up.
Indu
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nof
imm
une
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onse
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HIV
-1ca
nary
pox
viru
sA
LVA
CH
IV-1
and
gp12
0S
F-2
re-
com
bina
ntva
ccin
esin
unin
fect
edvo
lunt
eers
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IDS
12:2
407–
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,19
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[Ben
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Spe
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ains
tna
tive
orde
sia-
lyla
ted
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odefi
cien
cyvi
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JV
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693–
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Abs
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0cr
oss-
reac
twith
HIV
-2gp
140
due
toth
eim
mun
-od
omin
ante
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pein
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.
[Ber
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algl
eish
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4)]
A.B
eret
ta&
A.D
algl
eish
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elle
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pes.
AID
S8
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pl1)
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3–S
145,
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[Ber
etta
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7)]
A.
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etta
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Par
ravi
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,G
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ndro
nico
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opal
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S.B
utto
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itti,
G.B
.R
ossi
,G.V
iale
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li,&
A.G
.Sic
card
i.H
IVen
vG
lyco
prot
ein
Sha
res
aC
ross
-Rea
ctin
gE
pito
pew
itha
Sur
face
Pro
tein
Pre
sent
onA
ctiv
ated
Hum
anM
onoc
ytes
and
Invo
lved
inA
ntig
enP
rese
ntat
ion.Eu
rJ
Imm
un
ol1
7:17
93–
1798
,19
87.
(Med
line:
8808
3077
)N
otes
:T
heM
Ab
M38
bind
sto
gp12
0an
dal
soto
ahu
man
prot
ein
of80
kdth
atis
expr
esse
don
asm
allf
ract
ion
ofm
onon
ucle
arce
llsin
the
lym
phno
des.
M38
inhi
bits
prol
ifera
tion
inau
-to
logo
uste
tanu
sto
xoid
pres
enta
tion,
sois
invo
lved
inan
tigen
pres
enta
tion.
Sug
gest
edm
olec
ular
mim
icry
.
[Ber
man
(199
7)]
P.W
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man
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y,T.
Wrin
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.Ven
nari,
D.J
.Eas
t-m
an,G
.R.N
akam
ura,
D.P
.Fra
ncis
,G.G
orse
,&D
.H.S
chw
artz
.Gen
etic
and
imm
unol
ogic
char
acte
rizat
ion
ofvi
ruse
sin
fect
ing
MN
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120-
vacc
inat
edvo
lunt
eers
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fect
Dis
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384–
397,
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e:97
3793
81).
[Ber
man
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1)]
P.W
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erm
an,
K.
Ros
enth
al,
G.
Nak
amur
a,L.
Rid
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Por
ter,
D.
Dow
benk
o,M
.H
obbe
s,R
.B
yrn,
J.G
roop
man
,T.
Gre
gory
,&
B.
Fen
dly.
Mon
oclo
nala
ntib
odie
sto
gp16
0of
HIV
-1th
atne
utra
lize
HIV
-1
infe
ctiv
ity,
bloc
kth
ebi
ndin
gof
gp12
0to
CD
4,an
dre
act
with
dive
rse
isol
ates
.JA
IDS
4:30
6,19
91.
[Ber
thet
-Col
omin
as(1
999)
]C
.B
erth
et-C
olom
inas
,S
.M
onac
o,A
.N
ovel
li,G
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ai,F
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let,
&S
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ack.
Hea
d-to
-tai
ldim
ers
and
inte
rdom
ain
flexi
-bi
lity
reve
aled
byth
ecr
ysta
lstr
uctu
reof
HIV
-1ca
psid
prot
ein
p24
com
plex
edw
itha
mon
oclo
nalF
ab.EM
BO
18:1
124–
36,1
999.
(Med
line:
9916
4080
).
[Bin
ley
(199
9)]
J.B
inle
y,R
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ders
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las,
N.S
chue
lke,
A.M
aste
r,Y.
Guo
,F.
Kaj
umo,
D.
Ans
elm
a,P.
Mad
don,
W.
Ols
on,
&J.
Moo
re.
AR
ecom
bi-
nant
Hum
anIm
mun
odefi
cien
cyvi
rus
type
1en
velo
pegl
ycop
rote
inco
mpl
exst
abili
zed
byan
intr
amol
ecul
ardi
sulfi
debo
ndbe
twee
nth
egp
120
and
gp41
subu
nits
isan
antig
enic
mim
icof
the
trim
eric
virio
nas
soci
ated
stru
ctur
e.J
Viro
l74:
627–
43,1
999.
(Med
line:
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1317
).
[Bin
ley
(199
7a)]
J.M
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inle
y,H
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rsha
d,T.
R.
Fou
ts,
&J.
P.M
oore
.A
nin
vest
igat
ion
ofth
ehi
ghav
idity
antib
ody
resp
onse
togp
120
ofhu
man
im-
mun
odefi
cien
cyvi
rus
type
1.AID
SR
es
an
dH
um
an
Re
tro13
:100
7–10
15,
1997
a.(M
edlin
e:97
4075
38).
[Bin
ley
(199
6)]
J.M
.Bin
ley,
H.J
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el,C
.F.B
arba
sIII
,N.S
ulliv
an,J
.So-
dros
ki,P
.W.H
.I.P
arre
n,&
D.R
.Bur
ton.
Hum
anan
tibod
yre
spon
ses
toH
IVty
pe1
glyc
opro
tein
41cl
oned
inph
age
disp
lay
libra
ries
sugg
estt
hree
maj
orep
itope
sar
ere
cogn
ized
and
give
evid
ence
for
cons
erve
dan
tibod
ym
otifs
inan
tigen
bind
ing.
AID
SR
es
Hu
mR
etr
oviru
ses12:9
11–9
24,1
996.
(Med
-lin
e:96
3921
64)
Not
es:
Apa
nel
ofan
ti-gp
41hu
man
Fab
frag
men
tsw
ere
gene
rate
dby
pann
ing
phag
edi
spla
yan
tibod
ylib
rarie
spr
epar
edfr
omH
IV-1
posi
tive
dono
rsw
ithrg
p41.
Fab
ste
nded
tobe
dire
cted
agai
nstt
hree
epito
pes,
desi
gnat
edcl
uste
rsI-
III.
Non
ew
ere
neut
raliz
ing.
Aco
mm
onC
DR
3m
otif
was
foun
din
seve
ralo
fthe
heav
ych
ain
sequ
ence
s.
[Bin
ley
(199
7b)]
J.M
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inle
y,P.
J.K
lass
e,Y.
Cao
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Jone
s,M
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arko
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o,&
J.P.
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re.
Diff
eren
tialr
egul
atio
nof
the
antib
ody
resp
onse
sto
Gag
and
Env
prot
eins
ofhu
man
imm
unod
efici
ency
viru
sty
pe1.
JV
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71:2
799–
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b.(M
edlin
e:97
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46)
Not
es:
Ret
entio
nof
anti-
Env
antib
odie
san
dlo
ssof
anti-
Gag
antib
odie
sdu
ring
prog
ress
ion
was
stud
ied,
and
sugg
este
dto
beth
ere
sult
ofth
elo
ssof
T-ce
llhe
lpan
dth
eab
ility
ofE
nvto
stim
ulat
eB
cells
even
with
decl
inin
gC
D4
cells
,bec
ause
ofE
nv‘s
uniq
ueab
ility
tobi
ndto
the
CD
4m
olec
ule.
[Bin
ley
(199
8)]
J.M
.Bin
ley,
R.W
yatt,
E.D
esja
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s,P.
D.K
won
g,W
.Hen
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icks
on,J
.P.M
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Sod
rosk
i.A
naly
sis
ofth
ein
tera
ctio
nof
antib
odie
s
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-5D
EC
2000
with
aco
nser
ved
enzy
mat
ical
lyde
glyc
osyl
ated
core
ofth
eH
IVty
pe1
Env
e-lo
pegl
ycop
rote
in12
0.AID
SR
es
Hu
mR
etr
oviru
ses14:1
91–8
,199
8.(M
ed-
line:
9815
0872
)N
otes
:T
his
pape
rhe
lped
show
edth
ebi
olog
ical
rele
vanc
eof
ade
glyc
osyl
ated
varia
ble
loop
dele
ted
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eco
regp
120.
[Biz
ub-B
ende
r(1
994)
]D
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ub-B
ende
r,J.
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y,&
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lka.
Mon
-oc
lona
lant
ibod
ies
agai
nstH
IVty
pe1
Inte
gras
e:cl
ues
tom
olec
ular
stru
ctur
e.A
IDS
Re
sH
um
Re
trov
iru
ses10:1
105–
1115
,199
4.(M
edlin
e:95
1272
93).
[Bjo
rling
(199
2)]
E.
Bjo
rling
,L.
Goo
bar-
Lars
on,
G.
Utte
r,E
.N
orby
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F.C
hiod
i.F
our
dist
inct
antig
enic
regi
ons
are
pres
ent
inth
epr
imar
yst
ruc-
ture
ofH
IV-1
and
HIV
-2pr
otei
nase
s.AID
S6:
157–
163,
1992
.(M
edlin
e:92
2154
72).
[Boe
(199
8)]
S.O
.Boe
,B.B
jorn
dal,
B.R
osok
,A.M
.Szi
lvay
,&K
.H.K
alla
nd.
Sub
cellu
lar
loca
lizat
ion
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
RN
As,
Rev
,and
the
splic
ing
fact
orS
C-3
5.Viro
log
y24
4:47
3–82
,199
8.(M
edlin
e:98
2638
21).
[Bol
mst
edt(
1990
)]A
.Bol
mst
edt,
S.O
lofs
son,
E.S
jogr
en-J
anss
on,I
.Sjo
blom
,L.
Ake
rblo
m,
J.-E
.S
.H
anse
n,&
S.-
L.H
u.C
arbo
hydr
ate
dete
rmin
ant
Neu
Ac-
Galβ
(1-4
)of
N-li
nked
glyc
ans
mod
ulat
esth
ean
tigen
icac
tivity
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
glyc
opro
tein
gp12
0.JG
en
Viro
l73
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9–31
05,1
990.
(Med
line:
9310
7843
).
[Bol
mst
edt(
1996
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olm
sted
t,S
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jola
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E.
Han
sen,
L.A
kerb
lom
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.H
emm
ing,
S.
L.H
u,B
.M
orei
n,&
S.
Olo
fsso
n.In
fluen
ceof
N-li
nked
glyc
ans
inV
4-V
5re
gion
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
glyc
opro
-te
ingp
160
onin
duct
ion
ofa
viru
s-ne
utra
lizin
ghu
mor
alre
spon
se.
JA
IDS
Hu
mR
etr
oviro
l12:
213–
220,
1996
.(M
edlin
e:96
2756
29)
Not
es:
Bec
ause
N-li
nked
glyc
ans
onvi
ral
glyc
opro
tein
sca
npr
otec
tot
herw
ise
acce
ssib
lene
utra
lizat
ion
epito
pes
ofth
evi
rale
nvel
ope
from
neut
raliz
ing
antib
odie
s,th
eai
mof
this
stud
yw
asto
expl
ore
the
poss
ibili
tyof
achi
evin
ga
mor
ebr
oadl
yne
utra
lizin
gim
mun
ere
spon
sew
itha
gp16
0de
plet
edof
thre
eN
-lin
ked
glyc
ans
inth
eC
D4-
bind
ing
dom
ain.
Mut
ant
and
wild
type
gp16
0w
ere
form
ulat
edin
toim
mun
ostim
ulat
ing
com
plex
es(is
com
s),
and
guin
eapi
gsw
ere
vacc
inat
ed.
Bot
hpr
epar
atio
nsin
duce
dhi
ghse
rum
antib
ody
re-
spon
seto
nativ
egp
120
and
V3
pept
ides
.The
sera
from
anim
als
imm
uniz
edw
ithth
em
utat
edgl
ycop
rote
inla
ckin
gC
D4
glyc
osyl
atio
nsi
tes
did
notn
eu-
tral
ize
nonr
elat
edH
IVst
rain
sbe
tter
than
did
sera
from
anim
als
imm
uniz
edw
ithw
ildty
pegl
ycop
rote
in,
but
anim
als
imm
uniz
edw
ithm
utan
tgp
160
neut
raliz
edm
utan
tviru
sbe
tter
than
wild
type
viru
s,an
dvi
ceve
rsa.
[Boo
ts(1
997)
]L.
J.B
oots
,P.M
.McK
enna
,B.A
.Arn
old,
P.M
.Kel
ler,
M.K
.G
orny
,S
.Z
olla
-Paz
ner,
J.E
.R
obin
son,
&A
.J.
Con
ley.
Ant
i-hum
anim
-m
unod
efici
ency
viru
sty
pe1
hum
anm
onoc
lona
lan
tibod
ies
that
bind
dis-
cont
inuo
usep
itope
sin
the
vira
lgly
copr
otei
nsca
nid
entif
ym
imot
opes
from
reco
mbi
nant
phag
epe
ptid
edi
spla
ylib
rarie
s.AID
SR
es
Hu
mR
etr
oviru
ses
13:1
549–
59,1
997.
(Med
line:
9809
0112
).
[Bou
-Hab
ib(1
994)
]D
.C
.B
ou-H
abib
,G
.R
oder
ique
z,T.
Ora
vecz
,P.
W.
Ber
man
,P.
Luss
o,&
M.
A.
Nor
cros
s.C
rypt
icna
ture
ofen
velo
peV
3re
-gi
onep
itope
spr
otec
tspr
imar
ym
onoc
ytot
ropi
chu
man
imm
unod
efici
ency
viru
sty
pe1
from
antib
ody
neut
raliz
atio
n.JV
irol
68:6
006–
6013
,19
94.
(Med
line:
9433
5117
)N
otes
:T
his
pape
rsh
ows
that
antib
odie
sto
the
tipof
the
V3
loop
fail
tone
utra
lize
prim
ary
isol
ate
JR-C
SF,
and
that
the
V3
loop
isfa
rm
ore
acce
ssib
leon
the
JR-C
SF
deriv
edT-
cell
trop
icst
rain
T-C
SF.
Ant
i-V3
antib
odie
ssu
cces
sful
lyne
utra
lize
T-C
SF.
Wea
kbi
ndin
gof
anti-
V3
antib
odie
sto
the
prim
ary
isol
ate
JR-C
SF
sugg
ests
the
V3
loop
isac
cess
ible
only
ina
min
orfr
actio
nof
prot
eins
.
[Bou
det(
1995
)]F.
Bou
det,
H.K
elle
r,M
.P.K
ieny
,&J.
The
ze.
Sin
gle
pept
ide
and
anti-
idio
type
base
dim
mun
izat
ions
can
broa
den
the
antib
ody
resp
onse
agai
nst
the
varia
ble
V3
dom
ain
ofH
IV-1
inm
ice.M
olI
mm
un
ol3
2:44
9–45
7,19
95.
(Med
line:
9530
3114
)N
otes
:Giv
enth
ehi
ghde
gree
ofse
quen
ceva
riabi
lity
ofth
eV
3lo
op,
the
hum
oral
resp
onse
toth
isre
gion
tend
sto
bety
pesp
ecifi
c.A
nan
ti-id
ioty
pic
antib
ody
coul
dbr
oade
nth
ean
ti-V
3an
tibod
ypo
lycl
onal
resp
onse
inB
ALB
/cm
ice,
rela
tive
toth
eor
igin
alA
bus
edto
gene
rate
the
anti-
idio
type
resp
onse
.A
synt
hetic
pept
ide
deriv
edfr
omth
eV
3de
term
inan
tof
HIV
-1M
Nin
duce
dan
antib
ody
resp
onse
tom
ultip
leH
IV-1
stra
ins,
butt
heex
tent
ofth
iscr
oss-
reac
tivity
was
inve
rsel
yco
rrel
ated
with
the
bind
ing
affin
ityto
V3
MN
pept
ide.
[Bou
det(
1991
)]F.
Bou
det,
J.T
heze
,&
M.
Zou
ali.
UV
-tre
ated
poly
styr
ene
mic
rotit
repl
ates
foru
sein
anE
LIS
Ato
mea
sure
antib
odie
sag
ains
tsyn
thet
icpe
ptid
es.J
Imm
un
olM
eth
od
s142
:73–
82,1
991.
(Med
line:
1717
595)
.
[Bou
det(
1994
)]F.
Bou
det,
J.T
heze
,&M
.Zou
ali.
Ant
i-Idi
otyp
icA
ntib
odie
sto
the
Thi
rdVa
riabl
eD
omai
nof
gp12
0In
duce
anA
nti-H
IV-1
Ant
ibod
yR
espo
nse
inM
ice.V
irolo
gy
200:
176–
188,
1994
.(M
edlin
e:94
1747
15).
[Boy
er(1
991)
]V.
Boy
er,H
.Bro
ly,S
.Sou
che,
P.M
adau
le,J
.Ros
sier
,D.Z
a-gu
ry,
&C
.D
esgr
ange
s.C
hara
cter
izat
ion
and
larg
epr
oduc
tion
ofhu
man
mon
oclo
nal
antib
odie
sag
ains
tth
eH
IV-1
enve
lope
.C
linE
xpIm
mu
no
l83
:452
–459
,199
1.(M
edlin
e:91
1684
33).
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-6D
EC
2000
[Bra
dney
(199
9)]
A.
Bra
dney
,S
.S
chee
r,J.
Cra
wfo
rd,
S.
Buc
hbin
der,
&D
.Mon
tifior
i.N
eutr
aliz
atio
nes
cape
inhu
man
imm
unod
efici
ency
viru
sty
pe1-
infe
cted
long
term
non-
prog
ress
ors.JIn
fDis
179:
1264
–7,1
999.
(Med
line:
9920
8712
).
[Bra
nd(1
998)
]D
.B
rand
,F.
Lem
iale
,I.
Tur
bica
,L.
Buz
elay
,S
.B
rune
t,&
F.B
arin
.C
ompa
rativ
ean
alys
isof
hum
oral
imm
une
resp
onse
sto
HIV
type
1en
velo
pegl
ycop
rote
ins
inm
ice
imm
uniz
edw
itha
DN
Ava
ccin
e,re
com
bi-
nant
Sem
likiF
ores
tviru
sR
NA
,or
reco
mbi
nant
Sem
likiF
ores
tviru
spa
rti-
cles
.AID
SR
es
Hu
mR
etr
oviru
ses14:1
369–
77,1
998.
(Med
line:
9900
2727
).
[Bris
tow
(199
4)]
R.G
.W.B
risto
w,A
.R.D
ougl
as,J
.J.S
kehe
l,&
R.S
Dan
iels
.A
naly
sis
ofm
urin
ean
tibod
yre
spon
ses
toba
culo
viru
s-ex
pres
sed
hum
anim
-m
unod
efici
ency
viru
sty
pe1
enve
lope
glyc
opro
tein
s.J
Ge
nV
irol7
5:20
89–
2095
,19
94.
(Med
line:
9432
2004
)N
otes
:B
ALB
/cm
ice
wer
eim
mun
ized
with
bacu
lovi
rus
expr
esse
dgp
160
orgp
120,
and
15M
Abs
wer
ege
ner-
ated
.N
oM
Abs
gene
rate
din
this
stud
yne
utra
lized
refe
renc
est
rain
s,us
ing
ate
traz
oliu
m-b
ased
cyto
toxi
city
assa
yto
test
for
neut
raliz
atio
n.Te
nof
the
Mab
sw
ere
map
ped
bype
ptid
eE
LIS
A,a
ndse
ven
reac
ted
with
the
C1
regi
on,
one
with
V2,
one
with
V4,
and
one
with
the
C-t
erm
inal
end.
[Bro
der
(199
4)]
C.B
rode
r,P.
Ear
l,D
.Lon
g,S
.Abe
don,
B.M
oss,
&R
.Dom
s.A
ntig
enic
impl
icat
ions
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
enve
lope
quat
erna
ryst
ruct
ure:
Olig
omer
-spe
cific
and
-sen
sitiv
em
onoc
lona
lant
ibod
-ie
s.P
roc
Na
tlA
cad
Sci
US
A91:
1169
9–11
703,
1994
.(M
edlin
e:95
0623
36)
Not
es:
35an
ti-gp
41an
d27
anti-
gp12
0m
urin
eM
Abs
gene
rate
dby
imm
u-ni
zatio
nw
ithol
igom
eric
HIV
-1III
Ben
velo
pew
ere
stud
ied.
The
seM
Abs
tend
edto
reac
tw
ithco
nfor
mat
iona
lep
itope
s.21
ofth
ean
ti-gp
41M
Abs
reac
ted
pref
eren
tially
with
olig
omer
icen
v,w
hile
only
1of
the
anti-
gp12
0M
Abs
reac
ted
mor
est
rong
lyw
ithth
eol
igom
er,
and
14of
the
anti-
gp12
0pr
efer
entia
llyre
cogn
ized
mon
omer
icen
v.
[Bro
liden
(199
0)]
P.A
.B
rolid
en,
K.
Ljun
ggre
n,J.
Hin
kula
,E
.N
orrb
y,L.
Ake
rblo
m,&
B.W
ahre
n.A
mon
oclo
nala
ntib
ody
tohu
man
imm
unod
efi-
cien
cyvi
rus
type
1w
hich
med
iate
sce
llula
rcy
toto
xici
tyan
dne
utra
lizat
ion.
JV
irol6
4:93
6–94
0,19
90.
(Med
line:
9011
2670
).
[Bro
liden
(199
1)]
P.A
.Bro
liden
,B.M
akita
lo,L
.Ake
rblo
m,J
.Ros
en,K
.Bro
li-de
n,G
.Utte
r,M
.Jon
dal,
E.N
orrb
y,&
B.W
ahre
n.Id
entifi
catio
nof
amin
oac
ids
inth
eV
3re
gion
ofgp
120
criti
cal
for
viru
sne
utra
lizat
ion
byhu
-m
anH
IV-1
spec
ific
antib
odie
s.Imm
un
olo
gy7
3:37
1–37
6,19
91.
(Med
line:
9201
0009
).
[Bro
liden
(198
9)]
P.A
.Bro
liden
,V.M
osch
ese,
K.L
jung
gren
,J.R
osen
,C.F
un-
daro
,A.P
leba
ni,M
.Jon
dal,
&P.
Ros
si.
Dia
gnos
ticim
plic
atio
nof
spec
ific
imm
unog
lobu
linG
patte
rns
ofch
ildre
nbo
rnto
HIV
-1in
fect
edm
othe
rs.
AID
S3:
577,
1989
.(M
edlin
e:90
0007
45).
[Buc
hach
er(1
994)
]A
.B
ucha
cher
,R
.P
redl
,K
.S
trut
zenb
erge
r,W
.S
tein
fell-
ner,
A.T
rkol
a,M
.Pur
tsch
er,G
.Gru
ber,
C.T
auer
,F.S
tein
dl,A
.Jun
gbau
er,
&H
.Kat
inge
r.G
ener
atio
nof
hum
anm
onoc
lona
lant
ibod
ies
agai
nstH
IV-1
prot
eins
;ele
ctro
fusi
onan
dE
pste
in-B
arr
viru
str
ansf
orm
atio
nfo
rpe
riphe
ral
bloo
dly
mph
ocyt
eim
mor
taliz
atio
n.A
IDS
Re
sH
um
Re
trov
iru
ses10
:359
–36
9,19
94.
(Med
line:
9434
7460
)N
otes
:A
pane
lof
33hu
man
mon
oclo
nal
antib
odie
sw
ere
prod
uced
.Lin
eare
pito
pes
fors
ome
ofth
isse
tofM
Abs
wer
em
appe
dus
ing
pept
ide
ELI
SA
.Li
near
epito
pes
wer
em
appe
din
gp41
,an
da
sing
leep
itope
was
map
ped
inp2
4.W
hile
mul
tiple
gp12
0sp
ecifi
cM
Abs
wer
ege
nera
ted,
alls
eem
edto
beco
nfor
mat
iona
lorc
arbo
hydr
ate
depe
nden
t,or
both
.
[Buc
hach
er(1
992)
]A
.Buc
hach
er,R
.Pre
dl,C
.Tau
er,M
.Pur
tsch
er,G
.Gru
ber,
R.
Hei
der,
F.S
tein
dl,
A.
Trk
ola,
A.
Jung
baue
r,&
H.
Kat
inge
r.H
uman
mon
oclo
nala
ntib
odie
sag
ains
tgp4
1an
dgp
120
aspo
tent
iala
gent
sfo
rpas
sive
imm
uniz
atio
n.V
acc
ine
s92:
191–
195,
1992
.
[Buc
hbin
der
(199
2)]
A.B
uchb
inde
r,S
.Kar
wow
ska,
M.K
.Gor
ny,S
.T.B
urda
,&
S.
Zol
la-P
azne
r.S
yner
gyB
etw
een
Hum
anM
onoc
lona
lA
ntib
odie
sto
HIV
Ext
ends
The
irE
ffect
ive
Bio
logi
cA
ctiv
ityA
gain
stH
omol
ogou
san
dD
iver
gent
Str
ains
.AID
SR
es
Hu
mR
etr
oviru
ses8:42
5–42
7,19
92.
(Med
line:
9310
3824
)Not
es:T
hean
ti-gp
120
V3
MA
b44
7-D
and
the
anti-
gp12
0C
D4
BS
MA
b58
8-D
show
edsy
nerg
istic
neut
raliz
atio
n.
[Bug
ge(1
990)
]T.
H.B
ugge
,B.O
.Lin
dhar
dt,L
.L.H
anse
n,P.
Kus
k,E
.Hul
-ga
ard,
K.
Hol
mba
ck,
P.J.
Kla
sse,
J.Z
euth
en,
&K
.U
lrich
.A
naly
sis
ofa
Hig
hly
Imm
unod
omin
ant
Epi
tope
inth
eH
uman
Imm
unod
efici
ency
Viru
sTy
pe1
Tra
nsm
embr
ane
Gly
copr
otei
n,gp
41,
Defi
ned
bya
Hum
anM
ono-
clon
alA
ntib
ody.
JV
irol6
4:41
23–4
129,
1990
.(M
edlin
e:90
3478
03).
[Buk
awa
(199
5)]
H.
Buk
awa,
K.-
I.S
ekig
awa,
K.
Ham
ajim
a,J.
Fuk
ushi
ma,
Y.Y
amad
a,H
.Kiy
ono,
&K
.Oku
da.
Neu
tral
izat
ion
ofH
IV-1
byse
cret
ory
IgA
indu
ced
byor
alim
mun
izat
ion
with
ane
wm
acro
mol
ecul
arm
ultic
om-
pone
ntpe
ptid
eva
ccin
eca
ndid
ate.Na
ture
Me
d1:6
81–6
85,1
995.
(Med
line:
9607
1531
)N
otes
:Thi
spa
per
stud
ies
the
anti-
HIV
-1an
tibod
ies
rais
edin
re-
spon
seto
am
ultic
ompo
nent
pept
ide
vacc
ine,
give
nor
ally
.It
cons
iste
dof
:V
3lo
oppe
ptid
esba
sed
onse
quen
ces
from
cycl
ized
Bco
nsen
sus
sequ
ence
;
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-7D
EC
2000
aP
ND
com
mon
inJa
pan;
IIIB
PN
D;
Tha
iBst
rain
sP
ND
;a
CD
4bi
ndin
gsi
tepe
ptid
e;an
da
Gag
pept
ide,
HP
G30
.B
ALB
/cm
ice
wer
eim
mun
ized
.S
erum
IgA
and
IgG
and
feca
lIgA
wer
ede
tect
ed.
IgA
from
feca
lsam
ples
was
capa
ble
ofne
utra
lizin
gla
bst
rain
s.
[Bur
atti
(199
7)]
E.B
urat
ti,S
.G.T
ism
inet
zky,
P.D
’Aga
ro,&
F.E
.Bar
alle
.A
neut
raliz
ing
mon
oclo
nala
ntib
ody
prev
ious
lym
appe
dex
clus
ivel
yon
hum
anim
mun
odefi
cien
cyvi
rus
type
1gp
41re
cogn
izes
anep
itope
inp1
7sh
arin
gth
eco
rese
quen
ce.JV
irol7
1:24
57–6
2,19
97.
(Med
line:
9718
4581
).
[Bur
ton
(199
1)]
D.B
urto
n,C
.Bar
bas,
M.P
erss
on,S
.Koe
nig,
R.M
.Cha
nock
,&
R.A
.Ler
ner.
Ala
rge
arra
yof
hum
anm
onoc
lona
lant
ibod
ies
toty
pe1
hu-
man
imm
unod
efici
ency
viru
sfr
omco
mbi
nato
riall
ibra
ries
ofas
ympt
omat
icse
ropo
sitiv
ein
divi
dual
s.Pro
cN
atl
Aca
dS
ciU
SA8
8:10
134–
1013
7,19
91.
(Med
line:
9205
2225
)N
otes
:A
pane
lof
hum
anm
onoc
lona
lant
ibod
yF
abfr
agm
ents
was
gene
rate
dag
ains
tth
esu
rfac
eof
the
gp12
0gl
ycop
rote
inof
HIV
-1by
antig
ense
lect
ion
from
ara
ndom
com
bina
toria
llib
rary
prep
ared
from
5m
lofb
one
mar
row
from
anas
ympt
omat
icin
divi
dual
who
had
been
HIV
-pos
itive
for
6ye
ars.
The
seF
abva
riabl
ere
gion
sw
ere
sequ
ence
dan
dw
ere
foun
dto
bedi
vers
e.B
indi
ngco
nsta
nts
wer
em
easu
red
and
the
Fab
sge
nera
llybo
und
gp12
0w
ithhi
ghaf
finity
.T
hem
etho
dsus
edto
obta
inth
ispa
nelc
ould
beus
edto
obta
inan
tibod
ies
tote
stpa
ssiv
eim
mun
izat
ion
asa
ther
apy
for
AID
S.
[Bur
ton
&M
onte
fiori(
1997
)]D
.R.B
urto
n&
D.C
.Mon
tefio
ri.T
hean
tibod
yre
spon
sein
HIV
-1in
fect
ion.A
IDS
11S
uppl
A:S
87–S
98,1
997.
(Med
line:
9811
2351
)N
otes
:An
exce
llent
revi
ewof
Ab
epito
pes
and
the
impl
icat
ions
for
Env
elop
est
ruct
ure,
neut
raliz
atio
nof
HIV
,th
edi
stin
ctio
nbe
twee
npr
i-m
ary
and
TC
LAst
rain
s,A
DC
Can
dits
role
incl
eara
nce,
and
the
Ab
resp
onse
durin
gth
eco
urse
ofin
fect
ion.
[Bur
ton
(199
4)]
D.R
.Bur
ton,
J.P
yati,
R.K
odur
i,S
.J.S
harp
,G.B
.Tho
rnto
n,P.
W.
Par
ren,
L.S
.S
awye
r,R
.M
.H
endr
y,N
.D
unlo
p,&
P.L.
Nar
a.E
ffi-
cien
tne
utra
lizat
ion
ofpr
imar
yis
olat
esof
HIV
-1by
are
com
bina
nthu
man
mon
oclo
nala
ntib
ody.S
cie
nce
266:
1024
–102
7,19
94.
(Med
line:
9506
3934
)N
otes
:The
MA
bIg
G1b
12sh
owed
very
pote
ntne
utra
lizat
ion
ofa
rang
eof
prim
ary
Bsu
btyp
eis
olat
es.B
indi
ngw
itha
varie
tyof
inte
rnat
iona
liso
late
sw
aste
sted
;bou
ndto
mos
tBis
olat
es,2
0%of
A,C
and
Ds,
buth
ardl
yre
acte
dw
ithE
clad
e.
[Cal
arot
a(1
996)
]S
.Cal
arot
a,M
.Jan
sson
,M.L
evi,
K.B
rolid
en,O
.Lib
onat
ti,H
.Wig
zell,
&B
.Wah
ren.
Imm
unod
omin
antg
lyco
prot
ein
41ep
itope
iden
-
tified
byse
rore
activ
ityin
HIV
type
1-in
fect
edin
divi
dual
s.AID
SR
es
Hu
mR
etr
oviru
ses1
2:70
5–71
3,19
96.
(Med
line:
9630
3589
).
[Cao
(199
7)]
J.C
ao,N
.Sul
livan
,E.D
esja
rdin
,C.P
arol
in,J
.Rob
inso
n,R
.Wy-
att,
&J.
Sod
rosk
i.R
eplic
atio
nan
dne
utra
lizat
ion
ofhu
man
imm
unod
e-fic
ienc
yvi
rus
type
1la
ckin
gth
eV
1an
dV
2va
riabl
elo
ops
ofth
egp
120
Env
elop
egl
ycop
rote
in.J
Viro
lpag
es98
08–1
2,19
97.
(Med
line:
9803
7702
)N
otes
:A
nH
IV-1
mut
ant
lack
ing
the
V1-
V2
loop
sca
nre
plic
ate
inJu
rkat
cells
and
reve
rtan
tsth
atre
plic
ate
with
wild
-typ
eef
ficie
ncy
rapi
dly
evol
vein
cultu
re.T
hese
viru
ses
exhi
bite
din
crea
sed
neut
raliz
atio
nsu
scep
tibili
tyto
V3
loop
orC
D4i
MA
bs,
but
not
tosC
D4
oran
ti-C
D4B
SM
Abs
.T
hus
the
gp12
0V
1an
dV
2lo
ops
prot
ect
HIV
-1fr
omso
me
subs
ets
ofne
utra
lizin
gan
tibod
ies.
[Cap
on(8
9)]
D.J
.Cap
on,S
.M.C
ham
ow,J
.Mor
dent
i,S
.A.M
arst
ers,
T.G
re-
gory
,H.M
itsuy
a,R
.A.B
yrn,
C.L
ucas
,F.M
.Wur
m,J
.E.G
roop
man
,&et
al.
Des
igni
ngC
D4
imm
unoa
dhes
ins
forA
IDS
ther
apy.
Na
ture
337:
525–
31,8
9.(M
edlin
e:89
1275
15).
[Car
los
(199
9)]
M.
P.C
arlo
s,Y.
Yam
amur
a,F.
Dia
z-M
itom
a,&
J.V.
Torr
es.
Ant
ibod
ies
from
HIV
-pos
itive
and
AID
Spa
tient
sbi
ndto
anH
IVen
velo
pem
ultiv
alen
tvac
cine
.JA
cqu
irIm
mu
ne
De
ficS
ynd
r22:3
17–2
4,19
99.
(Med
-lin
e:20
0976
58).
[Cav
acin
i(19
93a)
]L.
A.
Cav
acin
i,C
.L.
Em
es,
J.P
ower
,A
.B
uchb
inde
r,S
.Zol
la-P
azne
r,&
M.R
.Pos
ner.
Hum
anm
onoc
lona
lant
ibod
ies
toth
eV
3lo
opof
HIV
-1gp
120
med
iate
varia
ble
and
dist
inct
effe
cts
onbi
ndin
gan
dvi
ral
neut
raliz
atio
nby
ahu
man
mon
oclo
nal
antib
ody
toth
eC
D4
bind
ing
site
.JA
IDS
6:35
3–35
8,19
93a.
(Med
line:
9320
4013
).
[Cav
acin
i(19
95)]
L.A
.C
avac
ini,
C.
L.E
mes
,J.
Pow
er,
F.D
.D
esha
rnai
s,M
.Duv
al,D
.Mon
tefio
ri,&
M.R
.Pos
ner.
Influ
ence
ofhe
avy
chai
nco
nsta
ntre
gion
son
antig
enbi
ndin
gan
dH
IV-1
neut
raliz
atio
nby
ahu
man
mon
oclo
nal
antib
ody.
JIm
mu
no
l155
:363
8–36
44,
1995
.(M
edlin
e:96
0160
13)
Not
es:
By
chan
ging
the
IgG
1co
nsta
ntre
gion
ofM
Ab
F10
5fr
omIg
G1κ
toIg
G3κ
,dr
amat
icst
rain
spec
ific
incr
ease
sin
neut
raliz
atio
nef
ficie
ncy
wer
eob
tain
ed.
[Cav
acin
i(19
94a)
]L.
A.C
avac
ini,
C.L
.Em
es,J
.Pow
er,M
.Duv
al,&
M.R
.P
osne
r.E
ffect
ofan
tibod
yva
lenc
yon
inte
ract
ion
with
cell-
surf
ace
expr
esse
dH
IV-1
and
vira
lneu
tral
izat
ion.J
Imm
un
ol1
52:2
538–
2545
,199
4a.(
Med
line:
9417
9837
).
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-8D
EC
2000
[Cav
acin
i(19
93b)
]L.
A.
Cav
acin
i,C
.L.
Em
es,
J.P
ower
,J.
Und
erda
lh,
R.
Gol
dste
in,
K.
May
er,
&M
.R
.P
osne
r.Lo
ssof
seru
man
tibod
ies
toa
conf
orm
atio
nale
pito
peof
HIV
-1/g
p120
iden
tified
bya
hum
anm
onoc
lona
lan
tibod
yis
asso
ciat
edw
ithdi
seas
epr
ogre
ssio
n.JA
IDS
6:10
93–1
102,
1993
b.(M
edlin
e:94
0159
13)
Not
es:
Ser
umfr
om10
0%of
asym
ptom
atic
HIV
-pos
itive
peop
lebl
ocke
dF
105
bind
ing,
whi
lese
rum
sam
ples
from
27%
ofA
RC
/AID
Spa
tient
sbl
ocke
dF
105
bind
ing.
[Cav
acin
i(19
98a)
]L.
A.
Cav
acin
i,C
.L.
Em
es,
A.
V.W
isne
wsk
i,J.
Pow
er,
G.
Lew
is,
D.
Mon
tefio
ri,&
M.
R.
Pos
ner.
Fun
ctio
nala
ndm
olec
ular
char
-ac
teriz
atio
nof
hum
anm
onoc
lona
lant
ibod
y.AID
SR
es
Hu
mR
etr
oviru
ses
14:1
271–
80,1
998a
.(M
edlin
e:98
4359
40).
[Cav
acin
i(19
94b)
]L.
A.C
avac
ini,
J.P
ower
,C.L
.Em
es,K
.Mac
e,G
.Tre
acy,
&M
.R.P
osne
r.P
lasm
aph
arm
acok
inet
ics
and
biol
ogic
alac
tivity
ofa
hum
anim
mun
odefi
cien
cyvi
rus
type
1ne
utra
lizin
ghu
man
mon
oclo
nal
antib
ody,
F10
5,in
cyno
mol
gus
mon
keys
.Tum
orI
mm
un
ol15
:251
–256
,199
4b.
(Med
-lin
e:94
3401
80)
Not
es:
MA
bF
105
was
adm
inis
tere
din
trav
enou
sly
tofo
urcy
nom
olgu
sm
onke
ys.A
t15
days
post
-dos
e,to
tals
erum
F10
5w
as23
0+
/-79
µg/
mla
ndF
105
was
imm
unor
eact
ive
with
cells
infe
cted
with
the
MN
and
IIIB
stra
ins
ofH
IV-1
asde
term
ined
byflo
wcy
tom
etry
.
[Cav
acin
i(19
98b)
]L.
A.C
avac
ini,
M.H
.Sam
ore,
J.G
ambe
rtog
lio,B
.Jac
kson
,M
.Duv
al,A
.Wis
new
ski,
S.H
amm
er,C
.Koz
iel,
C.T
rapn
ell,
&M
.R.P
osne
r.P
hase
Ist
udy
ofa
hum
anm
onoc
lona
lant
ibod
ydi
rect
edag
ains
tth
eC
D4-
.A
IDS
Re
sH
um
Re
trov
iru
ses14:5
45–5
0,19
98b.
(Med
line:
9825
2382
)Not
es:
Inan
imm
unot
hera
peut
icst
udy,
adm
inis
trat
ion
ofa
sing
ledo
seof
F10
5w
asno
n-to
xic
and
the
Ab
pers
iste
d,ye
tno
bene
fitw
asob
serv
edin
4in
divi
dual
s.T
heau
thor
ssu
gges
tit
may
bem
ore
help
fuli
not
her
setti
ngs,
for
exam
ple,
patie
nts
with
nopr
e-ex
istin
gan
ti-C
D4
BS
Abs
,ori
nco
mbi
natio
nw
ithot
her
MA
bs.
[Cav
acin
i(19
99)]
L.A
.Cav
acin
i,A
.Wis
new
ski,
J.E
.Pet
erso
n,D
.Mon
tefio
ri,C
.Em
es,M
.Duv
al,G
.Kin
gsbu
ry,A
.Wan
g,D
.Sca
dden
,&M
.R.P
osne
r.A
hum
anan
ti-H
IVau
toan
tibod
yen
hanc
esE
BV
tran
sfor
mat
ion
and
HIV
.C
linIm
mu
no
l93:
263–
73,1
999.
(Med
line:
2007
1224
).
[Cha
ng(1
998)
]A
.H
.C
hang
,J.
A.
Hox
ie,
S.
Cas
sol,
M.
O’S
haug
hnes
sy,
&F.
Jirik
.C
onst
ruct
ion
ofsi
ngle
-cha
inan
tibod
ies
that
bind
anov
erla
ppin
gep
itope
ofH
IV-1
Nef
.FE
BS
Le
tt441
:307
–12,
1998
.(M
edlin
e:99
0983
74).
[Cha
nh(1
987)
]T.
C.C
hanh
,G.R
.Dre
esm
an,&
R.C
.Ken
nedy
.M
onoc
lona
lan
ti-id
ioty
pic
antib
ody
mim
ics
the
CD
4re
cept
oran
dbi
nds
hum
anim
mun
-
odefi
cien
cyvi
rus.
Pro
cN
atl
Aca
dS
ciU
SA8
4:38
91–3
895,
1987
.(M
edlin
e:87
2319
23).
[Cha
nh(1
986)
]T.
C.
Cha
nh,
R.
C.
Ken
nedy
,B
.E
.A
lder
ete,
P.K
anda
,J.
W.
Eic
hber
g,&
G.
R.
Dre
esm
an.
Hum
anim
mun
odefi
cien
cyvi
rus
gp12
0gl
y-co
prot
ein
dete
cted
bya
mon
oclo
nala
ntib
ody
toa
synt
hetic
pept
ide.
Eu
rJ
Imm
un
ol1
6:14
65–1
468,
1986
.(M
edlin
e:87
0542
26).
[Che
n(1
995)
]C
.H.C
hen,
T.J.
Mat
thew
s,C
.B.M
cDan
al,D
.P.B
olog
nesi
,&M
.L.G
reen
berg
.A
mol
ecul
arcl
asp
inth
ehu
man
imm
unod
efici
ency
viru
s(H
IV)
type
1T
Mpr
otei
nde
term
ines
the
anti-
HIV
activ
ityof
gp41
deriv
a-tiv
es:
impl
icat
ion
for
vira
lfus
ion.
JV
irol6
9:37
71–3
777,
1995
.(M
edlin
e:95
2644
70).
[Che
n(1
996)
]J.
D.
Che
n,Q
.Y
ang,
W.
A.
Mar
asco
,&
S.
Y.C
hen.
Intr
a-an
dex
tra-
cellu
lar
imm
uniz
atio
nag
ains
tHIV
-1in
fect
ion
with
lym
phoc
ytes
tran
sduc
edw
ithan
AAV
vect
orex
pres
sing
ahu
man
anti-
gp12
0an
tibod
y.H
um
Ge
ne
Th
er7:
1515
–152
5,19
96.
(Med
line:
9701
8136
).
[Che
n(1
994a
)]S
.Y.
Che
n,Y.
Kho
uri,
J.B
agle
y,&
W.
A.
Mar
asco
.C
om-
bine
din
tra-
and
extr
acel
lula
rim
mun
izat
ion
agai
nst
hum
anim
mun
odefi
-ci
ency
viru
sty
pe1
infe
ctio
nw
itha
hum
anan
ti-gp
120
antib
ody.
Pro
cN
atl
Aca
dS
ciU
SA9
1:59
32–5
936,
1994
a.(M
edlin
e:94
2865
52).
[Che
n(1
994b
)]Y.
-H.C
hen,
A.S
usan
na,G
.Boc
k,F.
Ste
indl
,H
.Kat
inge
r,&
M.P
.Die
rich.
HIV
-1gp
41sh
ares
aco
mm
onim
mun
olog
icde
term
inan
twith
hum
anT,
Ban
dm
onoc
yte
cell
lines
.Imm
un
olL
ett
ers3
9:21
9–22
2,19
94b.
(Med
line:
9430
7758
)N
otes
:The
MA
b3D
6bi
nds
toH
IVgp
41,a
ndto
a43
kdpr
otei
nfo
und
inhu
man
T,B
and
mon
ocyt
ece
lllin
es.T
heau
thor
ssu
gges
tth
epo
ssib
ility
ofm
olec
ular
mim
icry
.
[Che
sebr
o&
Weh
rly(1
988)
]B
.C
hese
bro
&K
.W
ehrly
.D
evel
opm
ent
ofa
Sen
sitiv
eQ
uant
itativ
eF
ocal
Ass
ayfo
rH
uman
Imm
unod
efici
ency
Viru
sIn
-fe
ctiv
ity.
JV
irol6
2:37
79–3
788,
1988
.(M
edlin
e:88
3331
53).
[Che
sebr
o(1
992)
]B
.C
hese
bro,
K.
Weh
rly,
J.N
ishi
o,&
S.
Per
rym
an.
Mac
roph
age-
trop
ichu
man
imm
unod
efici
ency
viru
sis
olat
esfr
omdi
ffere
ntpa
tient
sex
hibi
tunu
sual
V3
enve
lope
sequ
ence
hom
ogen
eity
inco
mpa
rison
with
T-ce
ll-tr
opic
isol
ates
:defi
nitio
nof
criti
cala
min
oac
ids
invo
lved
ince
lltr
opis
m.J
Viro
l66:
6547
–54,
1992
.(M
edlin
e:93
0213
82).
[Chi
ba(1
997)
]J.
Chi
ba,
M.
Nak
ano,
Y.S
uzuk
i,K
.A
oyam
a,H
.O
hba,
T.K
obay
ashi
,A.Y
asud
a,A
.Koj
ima,
&T.
Kur
ata.
Gen
erat
ion
ofne
utra
lizin
g
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-9D
EC
2000
antib
ody
toth
ere
vers
etr
ansc
ripta
seof
hum
anim
mun
odefi
cien
cyvi
rus
type
1by
imm
uniz
ing
ofm
ice
with
anin
fect
ious
vacc
inia
viru
sre
com
bina
nt.
JIm
mu
no
lMe
tho
ds2
07:5
3–60
,199
7.(M
edlin
e:97
4691
14).
[Chi
n(1
995)
]L.
-T.
Chi
n,A
.-C
.M
alm
borg
,K
.K
riste
nsso
n,J.
Hin
kula
,B
.W
ahre
n,&
C.
A.
K.
Bor
reba
eck.
Mim
icki
ngth
ehu
mor
alim
mun
ere
-sp
onse
invi
tro
resu
ltsin
antig
en-s
peci
ficis
otyp
esw
itchi
ngsu
ppor
ted
bysp
ecifi
cau
tolo
gous
The
lper
cells
:gen
erat
ion
ofhu
man
HIV
-1-n
eutr
aliz
ing
IgG
mon
oclo
nala
ntib
odie
sfr
omna
ive
dono
rs.
Eu
rJ
Imm
un
ol2
5:65
7–66
3,19
95.
(Med
line:
9522
0411
).
[Cle
vela
nd(2
000a
)]S
.M.C
leve
land
,E.B
urat
ti,T.
D.J
ones
,P.N
orth
,F.B
ar-
alle
,L.M
cLai
n,T.
McI
nern
ey,Z
.Dur
rani
,&N
.J.D
imm
ock.
Imm
unog
enic
and
antig
enic
dom
inan
ceof
ano
nneu
tral
izin
gep
itope
over
ahi
ghly
con-
serv
edne
utra
lizin
gep
itope
inth
egp
41en
velo
pegl
ycop
rote
inof
hum
anim
mun
odefi
cien
cyvi
rus
type
1:its
dele
tion
lead
sto
ast
rong
neut
raliz
ing
resp
onse
.Viro
log
y26
6:66
–78,
2000
a.(M
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e:20
0809
74).
[Cle
vela
nd(2
000b
)]S
.M.C
leve
land
,T.D
.Jon
es,&
N.J
.Dim
moc
k.P
rope
rtie
sof
ane
utra
lizin
gan
tibod
yth
atre
cogn
izes
aco
nfor
mat
iona
lfor
mof
epito
peE
RD
RD
inth
egp
41C
-ter
min
alta
ilof
hum
anim
mun
odefi
cien
cyvi
rus
type
1.J
Ge
nV
irol8
1P
t5:1
251–
60,2
000b
.(M
edlin
e:20
2319
35).
[Col
lado
(200
0)]
M.C
olla
do,D
.Rod
rigue
z,J.
R.R
odrig
uez,
I.Va
zque
z,R
.M.
Gon
zalo
,&M
.Est
eban
.C
him
eras
betw
een
the
hum
anim
mun
odefi
cien
cyvi
rus
(HIV
-1)
Env
and
vacc
inia
viru
sim
mun
ogen
icpr
otei
nsp1
4an
dp3
9ge
nera
tein
mic
ebr
oadl
yre
activ
ean
tibod
ies
and
spec
ific
activ
atio
nof
CD
8+T
cell
resp
onse
sto
Env
.Vacc
ine1
8:31
23–3
3,20
00.
(Med
line:
2031
6327
).
[Con
ley
(199
4a)]
A.
J.C
onle
y,M
.K
.G
orny
,J.
A.
Kes
sler
II,L.
J.B
oots
,M
.Oss
orio
-Cas
tro,
S.K
oeni
g,D
.W.L
ineb
erge
r,E
.A.E
min
i,C
.Will
iam
s,&
S.
Zol
la-P
azne
r.N
eutr
aliz
atio
nof
prim
ary
hum
anim
mun
odefi
cien
cyvi
rus
type
1is
olat
esby
the
broa
dly
reac
tive
anti-
V3
mon
oclo
nala
ntib
ody
447-
52D
.JV
irol6
8:69
94–7
000,
1994
a.(M
edlin
e:95
0186
07).
[Con
ley
(199
6)]
A.
J.C
onle
y,J.
A.
Kes
sler
II,L.
J.B
oots
,P.
M.
McK
enna
,W
.A.S
chle
if,E
.A.E
min
i,G
.E.M
ark
III,H
.Kat
inge
r,E
.K.C
obb,
S.M
.Lu
ncef
ord,
S.
R.
Rou
se,
&K
.K
.M
urth
y.T
heco
nseq
uenc
eof
pass
ive
adm
inis
trat
ion
ofan
anti-
hum
anim
mun
odefi
cien
cyvi
rus
type
1ne
utra
lizin
gm
onoc
lona
lant
ibod
ybe
fore
chal
leng
eof
chim
panz
ees
with
apr
imar
yvi
rus
isol
ate.
JV
irol7
0:67
51–6
758,
1996
.(M
edlin
e:96
3865
62)N
otes
:The
MA
b2F
5w
asin
fuse
din
totw
och
impa
nzee
sw
hich
wer
eth
engi
ven
anin
trav
enou
s
chal
leng
ew
itha
prim
ary
HIV
-1is
olat
e–
both
beca
me
infe
cted
,bu
tw
ithde
laye
dde
tect
ion
and
prol
onge
dde
crea
sein
vira
lloa
dre
lativ
eto
cont
rols
,in
dica
ting
that
pree
xist
ing,
neut
raliz
ing
antib
odie
s(p
assi
vely
adm
inis
tere
dor
activ
ely
elic
ited)
affe
ctth
eco
urse
ofac
ute-
phas
evi
rus
repl
icat
ion
and
can
bein
fluen
tiala
fter
the
Ab
can
nolo
nger
bede
tect
edin
the
perip
hera
lci
rcul
atio
n.
[Con
ley
(199
4b)]
A.J
.Con
ley,
J.A
.Kes
sler
II,L.
J.B
oots
,J.-
S.T
ung,
B.A
.A
rnol
d,P.
M.K
elle
r,A
.R.S
haw
,&E
.A.E
min
i.N
eutr
aliz
atio
nof
dive
rgen
thu
man
imm
unod
efici
ency
viru
sty
pe1
varia
nts
and
prim
ary
isol
ates
byIA
M-
41-2
F5,
and
anti-
gp41
hum
anm
onoc
lona
lan
tibod
y.Pro
cN
atl
Aca
dS
ciU
SA
91:3
348–
3352
,199
4b.
(Med
line:
9421
1861
)N
otes
:2F
5is
capa
ble
ofne
utra
lizin
ga
broa
dra
nge
ofpr
imar
yis
olat
esan
dla
bst
rain
s.S
usce
ptib
ility
tone
utra
lizat
ion
was
depe
nden
ton
pres
ence
ofa
cons
erve
dan
tibod
ybi
ndin
gsi
te.K
inet
icst
udie
sw
ere
done
,and
2F5
has
ave
rylo
ngt
1/2
ofdi
ssoc
iatio
n,15
6m
inut
esfo
rgp
41.T
heau
thor
spo
into
utth
atLD
KW
core
ispr
esen
tin
high
lydi
verg
edin
tern
atio
nali
sola
tes.
[Con
nelly
(199
4)]
R.
J.C
onne
lly,
M.
Kah
n,J.
Bla
ke,
O.
K.
Haf
far,
&E
.K
.T
hom
as.
Dua
lspe
cific
ityof
am
onoc
lona
lant
i-idi
otyp
ican
tibod
yfo
rHIV
-1ne
utra
lizin
gm
onoc
lona
ls11
0.3
and
110.
4as
wel
las
the
V3
loop
ofgp
120.
Viro
log
y20
5:55
4–55
7,19
94.
(Med
line:
9506
5703
).
[Con
nor
(199
8)]
R.I
.Con
nor,
B.T
.Kor
ber,
B.S
.Gra
ham
,B.H
.Hah
n,D
.D.
Ho,
B.D
.Wal
ker,
A.U
.Neu
man
n,S
.H.V
erm
und,
J.M
este
cky,
S.J
acks
on,
E.
Fen
amor
e,Y.
Cao
,F.
Gao
,S
.K
alam
s,K
.J.
Kun
stm
an,
D.
McD
onal
d,N
.McW
illia
ms,
A.T
rkol
a,J.
P.M
oore
,&S
.M.W
olin
sky.
Imm
unol
ogic
alan
dvi
rolo
gica
lana
lyse
sof
pers
ons
infe
cted
byhu
man
imm
unod
efici
ency
viru
sty
pe1
whi
lepa
rtic
ipat
ing
intr
ials
ofre
com
bina
ntgp
120
subu
nitv
ac-
cine
s.J
Viro
l72:
1552
–76,
1998
.(M
edlin
e:98
1058
04)
Not
es:
No
gp12
0-va
ccin
ein
duce
dan
tibod
ies
ina
hum
antr
ialo
fgp
120
MN
and
SF
2co
uld
neut
raliz
eth
epr
imar
yvi
ruse
sth
atin
fect
edth
eva
ccin
ees.
The
prim
ary
iso-
late
sfr
omth
ein
fect
edva
ccin
ees
wer
esh
own
nott
obe
part
icul
arly
refr
activ
eto
neut
raliz
atio
nby
thei
rsu
scep
tibili
tyto
apa
nelo
fneu
tral
izin
gM
Abs
.
[Coo
k(1
994)
]D
.G.C
ook,
J.F
antin
i,S
.L.S
pita
lnik
,&F.
Gon
zale
z-S
cara
no.
Bin
ding
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
HIV
-1gp
120
toG
alac
-to
sylc
eram
ide
(Gal
Cer
):re
latio
nshi
pto
the
V3
loop
.V
irol
201:
206–
214,
1994
.(M
edlin
e:94
2408
06)N
otes
:Ant
ibod
ies
agai
nstG
alC
erca
nbl
ock
in-
fect
ion
ofC
D4-
nega
tive
cells
from
the
brai
nan
dco
lon
that
are
susc
eptib
leto
HIV
infe
ctio
n.T
his
pape
rex
plor
esth
eab
ility
ofa
pane
lofM
Abs
toin
hibi
t
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-10
DE
C20
00
bind
ing
ofgp
120
toG
alC
er,
and
also
ofth
ebi
ndin
gof
Gal
Cer
toin
hibi
tM
Ab-
gp12
0in
tera
ctio
n.M
Abs
toth
eV
3lo
opan
dG
alC
ersh
owed
mut
ual
inhi
bitio
nof
bind
ing
togp
120,
and
anti-
CD
4bi
ndin
gsi
teM
Abs
show
edre
-du
ced
inhi
bitio
n.N
-and
C-t
erm
inal
MA
bsdi
dn‘t
influ
ence
Gal
Cer
bind
ing.
[Cor
dell
(199
1)]
J.C
orde
ll,J.
P.M
oore
,C.J
.Dea
n,P.
J.K
lass
e,R
.A.W
eiss
,&
J.A
.McK
eatin
g.R
atm
onoc
lona
lant
ibod
ies
tono
nove
rlapp
ing
epito
pes
ofhu
man
imm
unod
efici
ency
viru
sty
peIg
p120
bloc
kC
D4
bind
ing
invi
tro.
Viro
log
y18
5:72
–79,
1991
.(M
edlin
e:92
0241
27).
[Cot
ropi
a(1
996)
]J.
Cot
ropi
a,K
.E.U
gen,
S.K
liks,
K.B
rolid
en,P
.-A
.Bro
li-de
n,J.
A.H
oxie
,V.S
rikan
tan,
W.V
.Will
iam
s,&
D.B
.Wei
ner.
AH
uman
Mon
oclo
nalA
ntib
ody
toH
IV-1
gp41
with
Neu
tral
izin
gA
ctiv
ityA
gain
stD
i-ve
rse
Labo
rato
ryIs
olat
es.JA
IDS
12:2
21–2
32,1
996.
(Med
line:
9627
5630
).
[Cot
ropi
a(1
992)
]J.
Cot
ropi
a,K
.E.U
gen,
D.L
ambe
rt,K
.Lju
nggr
en-B
rolid
en,
S.K
liks,
J.H
oxie
,&D
.B.W
eine
r.C
hara
cter
izat
ion
ofH
uman
Mon
oclo
nal
Ant
ibod
ies
toth
eH
IV-1
Tra
nsm
embr
ane
gp41
Pro
tein
.V
acc
ine
s9
2pag
es15
7–16
3,19
92.
Not
es:
Edi
tors
:F.
Bro
wn,
H.
S.
Gin
sber
gan
dR
.Le
rner
,C
old
Spr
ing
Har
bor
Labo
rato
ryP
ress
,Col
dS
prin
gH
arbo
r,N
Y.
[Cro
ix(1
993)
]D
.A
.C
roix
,H
.Y.
Yeh
,J.
Sed
lace
k,R
.B
.Lu
ftig,
&P.
D.
Got
tlieb
.A
dom
inan
tep
itope
ofH
IV-1
prot
ease
reco
gniz
edby
ham
ster
mon
oclo
nala
ntib
odie
s.JA
IDS
6:55
8–56
6,19
93.
(Med
line:
9326
7390
).
[Cru
iksh
ank
(199
7)]
W.W
.Cru
iksh
ank,
S.R
.Doc
trow
,M.S
.Fal
vo,K
.Huf
f-m
an,
J.M
acia
szek
,G
.V
iglia
nti,
J.R
aina
,H
.K
ornf
eld,
&B
.M
alfr
oy.
Alip
idat
edan
ti-Ta
tan
tibod
yen
ters
livin
gce
llsan
dbl
ocks
HIV
-1vi
ralr
epli-
catio
n.J
Acq
uir
Imm
un
eD
efic
Syn
dr
Hu
mR
etr
oviro
l14
:193
–203
,19
97.
(Med
line:
9723
2374
)Not
es:A
tech
niqu
ew
asde
velo
ped
tolip
idat
ean
tibod
-ie
san
dal
low
intr
acel
lula
rdel
iver
y;lip
idat
edan
ti-Ta
tinh
ibite
dvi
ralr
eplic
a-tio
nof
seve
ralH
IV-1
isol
ates
byap
prox
imat
ely
85%
assh
own
byin
crea
sed
viab
ility
ofin
fect
edce
llsan
dde
crea
sed
reve
rse
tran
scrip
tase
activ
ity.
[Dal
glei
sh(1
988)
]A
.G
.D
algl
eish
,T.
C.
Cha
nh,
R.
C.
Ken
nedy
,P.
Kan
da,
P.R
.Cla
pham
,&R
.A.W
eiss
.N
eutr
aliz
atio
nof
Div
erse
HIV
-1S
trai
nsby
Mon
oclo
nalA
ntib
odie
sR
aise
dag
ains
ta
gp41
Syn
thet
icP
eptid
e.V
irolo
gy
165:
209–
215,
1988
.(M
edlin
e:88
2658
60).
[De
San
tis(1
991)
]R
.D
eS
antis
,A
.A
nast
asi,
S.
Mar
colin
i,G
.Va
lesi
ni,
M.
Pez
zella
,N
.Vo
nesc
h,E
.S
turc
hio,
&A
.M
ele.
Pro
duct
ion
ofa
Nef
-sp
ecifi
cm
onoc
lona
lant
ibod
yby
the
use
ofa
synt
hetic
pept
ide.
AID
SR
es
an
dH
um
an
Re
trov
iru
ses7(
3):3
15–2
1,19
91.
(Med
line:
9129
1502
).
[del
Rea
l(19
99)]
G.
delR
eal,
M.
Llor
ente
,P.
Luca
s,L.
Kre
mer
,J.
L.To
ran,
&M
.-A
.C.
Ant
ibod
yre
pert
oire
agai
nstH
IV-1
gp12
0tr
igge
red
innu
dean
dno
rmal
mic
eby
GM
-CS
F/g
p120
imm
uniz
atio
n.Mo
lIm
mu
no
l36:
721–
31,
1999
.(M
edlin
e:20
0590
84).
[Den
isov
a(1
996)
]G
.Den
isov
a,B
.Ste
rn,D
.Rav
iv,J
.Zw
icke
l,N
.I.S
mor
odin
-sk
y,&
J.M
.G
ersh
oni.
Hum
oral
imm
une
resp
onse
toim
mun
ocom
plex
edH
IVen
velo
pegl
ycop
rote
in12
0.AID
SR
es
Hu
mR
etr
oviru
ses12:9
01–9
09,
1996
.(M
edlin
e:96
3921
63)N
otes
:Mic
ew
ere
inje
cted
with
the
gp12
0in
dif-
fere
ntco
nfigu
ratio
ns:f
ree,
com
plex
edw
ithC
D4,
and
asan
imm
unoc
ompl
exbo
und
toa
V3
loop
MA
b(M
77)
ofth
epr
otei
n.P
olyc
lona
lser
a,as
wel
las
mon
oclo
nala
ntib
odie
spr
oduc
edin
each
case
,wer
ean
alyz
ed.T
hefr
eegp
120
and
gp12
0-C
D4
com
plex
imm
unog
ens
stim
ulat
edre
spon
ses
wer
edi
rect
edm
ainl
yto
war
dco
nfor
mat
iona
lepi
tope
s,bu
tgp1
20im
mun
ocom
plex
edw
ithM
Ab
M77
also
prod
uced
num
erou
san
dva
ried
MA
bsdi
rect
edto
war
dlin
-ea
rep
itope
sth
atw
ere
pres
umab
lyin
acce
ssib
leon
the
gp12
0,gp
120-
CD
4pr
otei
ns.
[Den
isov
a(1
995)
]G
.Den
isov
a,J.
Zw
icke
l,&
J.M
.Ger
shon
i.B
indi
ngof
HIV
-1
gp12
0to
anan
ti-V
3lo
opan
tibod
yre
veal
sno
vela
ntig
en-in
duce
dep
itope
s.FA
SE
BJ9
:127
–132
,199
5.(M
edlin
e:95
1217
98)N
otes
:Thi
spa
perd
escr
ibes
the
char
acte
rizat
ion
offiv
ean
tibod
ies
that
bind
M77
-epi
tope
sth
atar
eon
lyre
veal
edup
onM
77-g
p120
inte
ract
ion.
[Den
isov
a(2
000)
]G
.F.D
enis
ova,
M.Z
erw
anitz
er,D
.A.D
enis
ov,E
.Spe
ctor
-m
an,I
.Mon
dor,
Q.S
atte
ntau
,&J.
M.G
ersh
oni.
Exp
ansi
onof
epito
pecr
oss-
reac
tivity
byan
ti-id
ioty
pem
odul
atio
nof
the
prim
ary
hum
oral
resp
onse
.M
ol
Imm
un
ol3
7:53
–8,2
000.
(Med
line:
2024
5598
).
[DeS
antis
(199
4)]
C.
DeS
antis
,L.
Lopa
lco,
P.R
obbi
oni,
R.
Long
hi,
G.
Rap
-po
ccio
lo,A
.G.S
icca
rdi,
&A
.Ber
etta
.H
uman
Ant
ibod
ies
toIm
mun
odom
i-na
ntC
5R
egio
nof
HIV
-1gp
120
Cro
ss-R
eact
with
HLA
Cla
ssIo
nA
ctiv
ated
Cel
ls.A
IDS
Re
sH
um
Re
trov
iru
ses10:1
57–1
62,1
994.
(Med
line:
9425
7320
).
[DeV
ico
(199
1)]
A.
L.D
eVic
o,T.
D.
Cop
elan
d,S
.O
rosz
lan,
R.
C.
Gal
lo,
&M
.G.S
arng
adha
ran.
Inte
ract
ion
ofC
-ter
min
alse
quen
ces
ofhu
man
imm
un-
odefi
cien
cyvi
rus
reve
rse
tran
scrip
tase
with
tem
plat
epr
imer
.J
Bio
lCh
em
266:
6774
–677
9,19
91.
(Med
line:
9120
1318
).
[Dev
ico
(199
5)]
A.
L.D
evic
o,R
.R
ahm
an,
J.W
elch
,R
.C
row
ley,
P.Lu
sso,
M.
G.
Sar
ngad
hara
n,&
R.
Pal
.M
onoc
lona
lant
ibod
ies
rais
edag
ains
tco
-va
lent
lycr
ossl
inke
dco
mpl
exes
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-11
DE
C20
00
gp12
0an
dC
D4
rece
ptor
iden
tify
ano
vel
com
plex
-dep
ende
ntep
itope
ongp
120.
Viro
log
y21
1:58
3–58
8,19
95.
(Med
line:
9537
3192
)N
otes
:To
ex-
plor
eth
eim
mun
ogen
icity
ofre
gion
sof
gp12
0th
atar
eex
pose
ddu
eto
conf
or-
mat
iona
lcha
nges
ingp
120
upon
CD
4bi
ndin
g,C
D4
was
cova
lent
lylin
ked
togp
120
and
this
com
plex
was
used
asan
imm
unog
enfo
rB
ALB
/cm
ice.
Two
MA
bsw
ere
prod
uced
,bot
hof
whi
chbi
ndpr
efer
entia
llyto
the
gp12
0-C
D4
com
plex
,and
are
conf
orm
atio
nal.
Com
petit
ion
assa
ysin
dica
teth
ese
MA
bsbi
ndto
epito
pes
that
are
reco
gniz
edby
sera
from
HIV
-1in
fect
edhu
man
s.
[diM
arzo
Vero
nese
(198
6)]
F.di
Mar
zoVe
rone
se,T
.D.C
opel
and,
A.L
.De-
Vic
o,R
.R
ahm
an,
S.O
rosz
lan,
R.
C.
Gal
lo,
&M
.G
.S
arng
adha
ran.
Cha
r-ac
teriz
atio
nof
high
lyim
mun
ogen
icp6
6/p5
1as
the
reve
rse
tran
scrip
tase
ofH
TLV
-III/
LAV
.S
cie
nce
231:
1289
–129
1,19
86.(
Med
line:
8612
2937
)Not
es:
Thi
sst
udy
iden
tified
the
66an
d51
kilo
dalto
nsba
nds
inw
este
rnbl
ots
asR
T.E
nzym
atic
activ
ityw
assh
own,
and
the
prot
ein
was
defin
edby
Edm
und
N-
term
inal
degr
adat
ion
and
com
paris
onto
HIV
-1po
lnuc
leot
ide
tran
slat
ion.
Am
ouse
hybr
idom
aw
asge
nera
ted
that
inhi
bite
den
zym
eac
tivity
.
[diM
arzo
Vero
nese
(199
2)]
F.di
Mar
zoVe
rone
se,
R.
Rah
man
,R
.P
al,
C.B
oyer
,J.R
oman
o,V.
S.K
alya
nara
man
,B.C
.Nai
r,R
.C.G
allo
,&M
.G.
Sar
ngad
hara
n.D
elin
eatio
nof
imm
unor
eact
ive,
cons
erve
dre
gion
sin
the
ex-
tern
alen
velo
pegl
ycop
rote
inof
the
hum
anim
mun
odefi
cien
cyvi
rus
type
1.A
IDS
Re
sH
um
Re
trov
iru
ses8:11
25–1
132,
1992
.(M
edlin
e:92
3687
30).
[diM
arzo
Vero
nese
(199
3)]
F.di
Mar
zoVe
rone
se,M
.S.R
eitz
and,
G.G
upta
,M
.Rob
ert-
Gur
off,
C.B
oyer
-Tho
mps
on,A
.Lou
ie,R
.C.G
allo
,&P.
Luss
o.Lo
ssof
ane
utra
lizin
gep
itope
bya
spon
tane
ous
poin
tm
utat
ion
inth
eV
3lo
opof
HIV
-1is
olat
edfr
oman
infe
cted
labo
rato
ryw
orke
r.JB
iol
Ch
em
268:
2589
4–25
901,
1993
.(M
edlin
e:94
0646
68)
Not
es:T
heM
Ab
M77
can-
not
neut
raliz
ea
viru
sis
olat
edfr
oma
IIIB
infe
cted
lab-
wor
ker
that
has
asi
ngle
poin
tmut
atio
nin
the
defin
edlin
ear
epito
pe.M
77ca
nnot
bind
toth
em
utan
tnat
ive
gp12
0,bu
tcan
bind
toa
pept
ide
that
carr
ies
the
subs
titut
ion.
[diM
arzo
Vero
nese
(198
5)]
F.di
Mar
zoVe
rone
se,
M.
G.
Sar
ngad
hara
n,R
.R
ahm
an,
P.D
.M
arkh
am,
M.
Pop
ovic
,A
.J.
Bod
ner,
&R
.C
.G
allo
.M
onoc
lona
lant
ibod
ies
spec
ific
for
p24,
the
maj
orco
repr
otei
nof
hum
anT-
cell
leuk
emia
viru
sty
peIII
.Pro
cN
atl
Aca
dS
ciU
SA8
2:51
99–5
202,
1985
.(M
edlin
e:85
2704
92).
[Dic
key
(200
0)]
C.D
icke
y,U
.Zie
gner
,M.G
.Aga
djan
yan,
V.S
rikan
tan,
Y.R
e-fa
eli,
A.
Pra
bhu,
A.
Sat
o,W
.V.
Will
iam
s,D
.B
.W
eine
r,&
K.
E.
Uge
n.M
urin
em
onoc
lona
lant
ibod
ies
biol
ogic
ally
activ
eag
ains
tthe
amin
ore
gion
ofH
IV-1
gp12
0:is
olat
ion
and
char
acte
rizat
ion.D
NA
Ce
llB
iol1
9:24
3–52
,20
00.
(Med
line:
2025
6306
).
[Din
gwal
l(19
89)]
C.
Din
gwal
l,I.
Ern
berg
,M
.J.
Gai
t,S
.M
.G
reen
,S
.H
ea-
phy,
J.K
arn,
A.D
.Low
e,M
.Sin
gh,M
.A.S
kinn
er,&
R.V
aler
io.
Hum
anim
mun
odefi
cien
cyvi
rus
1ta
tpr
otei
nbi
nds
tran
s-ac
tivat
ion-
resp
onsi
vere
-gi
on(T
AR
)R
NA
invi
tro.
Pro
cN
atl
Aca
dS
ciU
SA8
6:69
25–6
929,
1989
.(M
edlin
e:89
3866
52).
[Ditz
el(1
995)
]H
.J.D
itzel
,J.M
.Bin
ley,
J.P.
Moo
re,J
.Sod
rosk
i,N
.Sul
livan
,L.
S.
W.
Saw
yer,
R.
M.
Hen
dry,
W.-
P.Y
ang,
C.
F.B
arba
sIII
,&
D.
R.
Bur
ton.
Neu
tral
izin
gre
com
bina
nthu
man
antib
odie
sto
aco
nfor
mat
iona
lV
2-an
dC
D4-
bind
ing
site
-sen
sitiv
eep
itope
ofH
IV-1
gp12
0is
olat
edby
usin
gan
epito
pe-m
aski
ngpr
oced
ure.J
Imm
un
ol1
54:8
93–9
06,
1995
.(M
edlin
e:95
1144
16)
Not
es:
Apa
nel
ofF
abs
was
obta
ined
from
alib
rary
prep
ared
from
the
bone
mar
row
ofa
long
-ter
mas
ympt
omat
icH
IV-1
sero
posi
tive
mal
edo
nor.
Fou
rF
abs
reco
gniz
eth
eC
D4B
S.A
nad
ditio
nalf
our
Fab
sw
ere
retr
ieve
daf
tere
pito
pem
aski
nggp
120
with
the
CD
4BS
Fab
sat
the
scre
enin
gst
age.
3/4
ofth
ese
Fab
sbi
ndto
aV
2de
pend
entc
onfo
rmat
iona
lepi
tope
.
[Ditz
el(1
997)
]H
.J.D
itzel
,P.W
.Par
ren,
J.M
.Bin
ley,
J.S
odro
ski,
J.P.
Moo
re,
C.
F.B
.3r
d,&
D.
R.
Bur
ton.
Map
ping
the
prot
ein
surf
ace
ofhu
man
im-
mun
odefi
cien
cyvi
rus
type
1gp
120
usin
ghu
man
mon
oclo
nal
antib
odie
sfr
omph
age
disp
lay
libra
ries.
JM
ol
Bio
l26
7:68
4–95
,19
97.
(Med
line:
9727
2001
)N
otes
:(G
enba
nk:
U82
767
U82
768
U82
769
U82
770
U82
771
U82
772
U82
942
U82
943
U82
944
U82
945
U82
946
U82
947
U82
948
U82
949
U82
950
U82
951
U82
952
U82
961
U82
962)
Rec
ombi
nant
mon
o-cl
onal
antib
odie
sfr
omph
age
disp
lay
libra
ries
prov
ide
am
etho
dfo
rEnv
sur-
face
epito
pem
appi
ng.
Div
erse
epito
pes
are
acce
ssed
bypr
esen
ting
gp12
0to
the
libra
ryin
diffe
rent
form
s,su
chas
sequ
entia
lm
aski
ngof
epito
pes
with
exis
ting
MA
bsor
sCD
4pr
ior
tose
lect
ion
orby
sele
ctio
non
pept
ides
.F
abs
iden
tified
byth
ese
met
hods
have
spec
ifici
ties
asso
ciat
edw
ithep
itope
spr
esen
ted
poor
lyon
nativ
em
ultim
eric
enve
lope
.
[Dow
benk
o(1
988)
]D
.D
owbe
nko,
G.
Nak
amur
a,C
.F
enni
e,C
.S
him
asak
i,L.
Rid
dle,
R.
Har
ris,
T.G
rego
ry,
&L.
Lask
y.E
pito
pem
appi
ngof
the
imm
unod
efici
ency
viru
sty
pe1
gp12
0w
ithm
onoc
lona
lant
ibod
ies.
JV
irol
62:4
703–
4711
,198
8.(M
edlin
e:89
0373
59).
[D’S
ouza
(199
1)]
M.P
.D’S
ouza
,P.D
urda
,C.V
.Han
son,
G.M
ilman
,&C
.In-
vest
igat
ors.
Eva
luat
ion
ofm
onoc
lona
lant
ibod
ies
toH
IV-1
byne
utra
lizat
ion
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-12
DE
C20
00
and
sero
logi
cala
ssay
s:an
inte
rnat
iona
lcol
labo
ratio
n.A
IDS
5:10
61–1
070,
1991
.(M
edlin
e:92
0297
21).
[D’S
ouza
(199
4)]
M.
P.D
’Sou
za,
S.
J.G
eyer
,C
.V.
Han
son,
R.
M.
Hen
dry,
G.
Milm
an,
&C
.In
vest
igat
ors.
Eva
luat
ion
ofm
onoc
lona
lan
tibod
ies
toH
IV-1
enve
lope
byne
utra
lizat
ion
and
bind
ing
assa
ys:
anin
tern
atio
nalc
ol-
labo
ratio
n.A
IDS
8:16
9–18
1,19
94.
(Med
line:
9431
8200
).
[D’S
ouza
(199
5)]
M.P
.D’S
ouza
,G.M
ilman
,J.A
.Bra
dac,
D.M
cPhe
e,C
.V.
Han
son,
&R
.M
.H
endr
y.N
eutr
aliz
atio
nof
prim
ary
HIV
-1is
olat
esby
anti-
enve
lope
mon
oclo
nal
antib
odie
s.AID
S9:
867–
874,
1995
.(M
edlin
e:96
0149
59)N
otes
:Ele
ven
labs
test
edth
e6
hum
anM
Abs
1125
H,T
H9,
4.8D
,25
7-D
-IV,
TH
1,2F
5,an
dal
soH
IVIG
for
neut
raliz
atio
nof
MN
,JR
CS
F,th
etw
oB
clad
epr
imar
yis
olat
es30
1657
and
TH
A/9
2/02
6,an
dth
eD
clad
eis
olat
eU
G/9
2/21
.2F
5w
asth
em
ostb
road
lyne
utra
lizin
g,be
tter
than
HIV
IG.T
heot
her
MA
bssh
owed
limite
dne
utra
lizat
ion
ofon
lyM
N(a
nti-C
D4B
SM
Abs
1125
H,T
H9,
and
4.8D
),or
MN
and
JRC
SF
(ant
i-V3
MA
bs25
7-D
-IV
and
TH
1).
[D’S
ouza
(199
7)]
P.D
’Sou
za,
D.
Livn
at,
J.A
.B
rada
c,S
.H
.B
ridge
san
dth
eA
IDS
Clin
ical
Tria
lsG
roup
Ant
ibod
yS
elec
tion
Wor
king
Gro
up,&
C.I
nves
-tig
ator
s.E
valu
atio
nof
mon
oclo
nala
ntib
odie
sto
hum
anim
mun
odefi
cien
cyvi
rus
type
1pr
imar
yis
olat
esby
neut
raliz
atio
nas
says
:per
form
ance
crite
riafo
rse
lect
ing
cand
idat
ean
tibod
ies
for
clin
ical
tria
ls.
JIn
fect
Dis
175:
1056
–10
62,
1997
.(M
edlin
e:97
2751
72)
Not
es:
Fiv
ela
bora
torie
sev
alua
ted
neu-
tral
izat
ion
ofni
nepr
imar
yB
clad
eis
olat
esby
aco
ded
pane
lofs
even
hum
anM
Abs
toH
IV-1
subt
ype
Ben
velo
pe.
IgG
1b12
,2G
12,
2F5
show
edpo
tent
and
broa
dly
cros
s-re
activ
ene
utra
lizin
gab
ility
;F10
5,44
7/52
-D,7
29-D
,19b
did
notn
eutr
aliz
eth
epr
imar
yis
olat
es.
[Dua
rte
(199
4)]
C.A
.Dua
rte,
M.M
onte
ro,A
.Ser
alen
a,R
.Val
des,
V.Ji
men
ez,
J.B
enite
z,E
.N
arci
andi
,J.
Mad
razo
,G
.P
adro
n,G
.S
anch
ez,
G.
Gill
-ja
m,
K.
Per
sson
,S
.O
jeda
,A
.C
abal
lero
,A
.M
irand
a,M
.C
.D
omin
guez
,B
.W
ahre
n,&
A.
Men
ende
z.M
ultie
pito
pepo
lype
ptid
eof
the
HIV
-1en
ve-
lope
indu
ces
neut
raliz
ing
mon
oclo
nala
ntib
odie
sag
ains
tV3
loop
.A
IDS
Re
sH
um
Re
trov
iru
ses1
0:23
5–24
3,19
94.
(Med
line:
9428
9061
).
[Dur
da(1
990)
]P.
J.D
urda
,L.B
ache
ler,
P.C
laph
am,A
.M.J
enos
ki,B
.Lee
ce,
T.J.
Mat
thew
s,A
.McK
nigh
t,R
.Pom
eran
tz,M
.Ray
ner,
&K
.J.W
einh
old.
HIV
-1ne
utra
lizin
gm
onoc
lona
lant
ibod
ies
indu
ced
bya
synt
hetic
pept
ide.
AID
SR
es
Hu
mR
etr
oviru
ses6:11
15,1
990.
(Med
line:
9109
0986
).
[Dur
da(1
988)
]P.
J.D
urda
,B
.Le
ece,
A.
M.
Jeno
ski,
H.
Rab
in,
A.
Fis
her,
R.
Gal
lo,
&F.
Won
g-S
taal
.C
hara
cter
izat
ion
ofm
urin
em
onoc
lona
lan
ti-bo
dies
toH
IV-1
indu
ced
bysy
nthe
ticpe
ptid
es.
AID
SR
es
Hu
mR
etr
oviru
ses
4:33
1–34
2,19
88.
(Med
line:
8906
2029
).
[Dur
rani
(199
8)]
Z.D
urra
ni,T
.L.M
cIne
rney
,L.M
cLai
n,T.
Jone
s,T.
Bel
laby
,F.
R.
Bre
nnan
,&
N.
J.D
imm
ock.
Intr
anas
alim
mun
izat
ion
with
apl
ant
viru
sex
pres
sing
ape
ptid
efr
omH
IV-1
gp41
stim
ulat
esbe
tter
muc
osal
and
syst
emic
HIV
-1-s
peci
ficIg
Aan
dIg
Gth
anor
alim
mun
izat
ion.J
Imm
un
ol
Me
tho
ds2
20:9
3–10
3,19
98.
(Med
line:
9905
3665
).
[Ear
l(19
97)]
P.L.
Ear
l,C
.C.B
rode
r,R
.W.D
oms,
&B
.Mos
s.E
pito
pem
apof
hum
anim
mun
odefi
cien
cyvi
rus
type
1gp
41de
rived
from
47m
onoc
lona
lan
tibod
ies
prod
uced
byim
mun
izat
ion
with
olig
omer
icen
velo
pepr
otei
n.J
Viro
l71:
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–84,
1997
.(M
edlin
e:97
2139
31).
[Ear
l(19
94)]
P.L.
Ear
l,C
.C
.B
rode
r,D
.Lo
ng,
S.
A.
Lee,
J.P
eter
son,
S.C
hakr
abar
ti,R
.W.D
oms,
&B
.Mos
s.N
ativ
eol
igom
eric
hum
anim
mun
od-
efici
ency
viru
sty
pe1
Env
elop
egl
ycop
rote
inel
icits
dive
rse
mon
oclo
nala
nti-
body
reac
tiviti
es.J
Viro
l68:
3015
–302
6,19
94.
(Med
line:
9420
2289
)Not
es:
Ina
stud
yof
the
repe
rtoi
reof
resp
onse
tool
igom
eric
vers
usm
onom
eric
Env
prot
ein,
138
mur
ine
MA
bsw
ere
gene
rate
din
resp
onse
toan
imm
uno-
gen
that
was
agp
120/
bp41
olig
omer
icm
olec
ule
that
was
not
clea
ved
due
toa
mut
atio
nin
the
clea
vage
site
.T
heol
igom
eric
mol
ecul
ew
asfo
und
toel
icit
are
spon
seth
atw
asve
rydi
ffere
ntth
anth
em
onom
er.M
ostM
Abs
wer
eco
nfor
mat
iona
l,m
any
wer
eto
gp41
orif
ingp
120,
toth
eC
D4
BS
.F
ewM
Abs
tolin
ear
V3
epito
pes
wer
epr
oduc
edin
resp
onse
tool
igom
eric
pro-
tein
,tho
ugh
this
was
aco
mm
onsp
ecifi
city
inre
spon
seto
imm
uniz
atio
nw
ithgp
120
mon
omer
icpr
otei
n.
[Eat
on(1
994)
]A
.M
.E
aton
,K
.E
.U
gen,
D.
B.
Wei
ner,
T.W
ildes
,&
J.A
.Le
vy.
An
Ant
i-gp4
1H
uman
Mon
oclo
nal
Ant
ibod
yT
hat
Enh
ance
sH
IV-
1In
fect
ion
inth
eA
bsen
ceof
Com
plem
ent.AID
SR
es
Hu
mR
etr
oviru
ses
10:1
3–18
,199
4.(M
edlin
e:94
2353
68).
[Edd
lest
on(1
993)
]M
.E
ddle
ston
,J.
C.
dela
Torr
e,J.
-Y.
Xu,
N.
Dor
fman
,A
.N
otki
ns,
S.
Zol
la-P
azne
r,&
M.
B.
A.
Old
ston
e.M
olec
ular
Mim
icry
Acc
ompa
nyin
gH
IV-1
Infe
ctio
n:H
uman
Mon
oclo
nalA
ntib
odie
sT
hatB
ind
togp
41an
dto
Ast
rocy
tes.A
IDS
Re
sH
um
Re
trov
iru
ses10:9
39–9
44,1
993.
(Med
line:
9410
7594
)N
otes
:In
this
pape
r,th
ree
anti-
HIV
-1gp
41sp
ecifi
cM
Abs
wer
efo
und
tore
actw
ithas
troc
ytes
:98-
6,16
7-7
and
15G
1.R
eact
ive
astr
ocyt
esin
the
hipp
ocam
pus
wer
em
ost
prom
inen
tlyin
volv
ed,
and
the
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-13
DE
C20
00
antib
odie
sst
aine
dno
othe
rce
llty
pein
the
brai
n,ki
dney
orliv
er.
All
thre
em
appe
dto
aco
nfor
mat
iona
llyde
pend
ente
pito
pebe
twee
naa
644-
663.
[Ehr
hard
(199
6)]
B.
Ehr
hard
,R
.M
isse
lwitz
,K
.W
elfle
,G
.H
ausd
orf,
R.
W.
Gla
ser,
J.S
chne
ider
-Mer
gene
r,&
H.W
elfle
.C
hem
ical
mod
ifica
tion
ofre
-co
mbi
nant
HIV
-1ca
psid
prot
ein
p24
lead
sto
the
rele
ase
ofa
hidd
enep
itope
prio
rto
chan
ges
ofth
eov
eral
lfol
ding
ofth
epr
otei
n.Bio
che
mis
try3
5:90
97–
9105
,199
6.(M
edlin
e:96
2912
51).
[Em
ini(
1992
)]E
.A.E
min
i,W
.A.S
chle
if,J.
H.N
unbe
rg,A
.J.C
onle
y,Y.
Eda
,S
.To
kiyo
shi,
S.
D.
Put
ney,
S.
Mat
sush
ita,
K.
E.
Cob
b,C
.M
.Je
tt,J.
W.
Eic
hber
g,&
K.
K.
Mur
thy.
Pre
vent
ion
ofH
IV-1
infe
ctio
nin
chim
panz
ees
bygp
120
V3
dom
ain-
spec
ific
mon
oclo
nala
ntib
ody.Na
ture
355:
728–
730,
1992
.(M
edlin
e:92
1580
79).
[Ern
st(1
998)
]W
.E
rnst
,R
.G
rabh
err,
D.
Weg
ner,
N.
Bor
th,
A.
Gra
ssau
er,
&H
.K
atin
ger.
Bac
ulov
irus
surf
ace
disp
lay:
cons
truc
tion
and
scre
enin
gof
aeu
kary
otic
epito
pelib
rary
.Nu
cle
icA
cid
sR
es26
:171
8–23
,199
8.(M
edlin
e:98
1810
76).
[Eva
ns(1
989)
]D
.J.E
vans
,J.M
cKea
ting,
J.M
.Mer
edith
,K.L
.Bur
ke,K
.Ka-
trak
,A.J
ohn,
M.F
ergu
son,
P.D
.Min
or,R
.A.W
eiss
,&J.
W.A
lmon
d.A
nen
gine
ered
polio
viru
sch
imer
ael
icits
broa
dly
reac
tive
HIV
-1ne
utra
lizin
gan
tibod
ies.
Na
ture
339:
385–
388,
1989
.(M
edlin
e:89
2620
52).
[Fai
man
&H
orov
itz(1
997)
]G
.A
.F
aim
an&
A.
Hor
ovitz
.T
herm
odyn
amic
anal
ysis
ofth
ein
tera
ctio
nbe
twee
nth
e0.
5bet
aF
vfr
agm
enta
ndth
eR
P13
5pe
ptid
ean
tigen
deriv
edfr
omth
eV
3lo
opof
HIV
-1
gp12
0.JB
iolC
he
m27
2:31
407–
11,1
997.
(Med
line:
9805
8925
).
[Fel
genh
auer
(199
0)]
M.
Fel
genh
auer
,J.
Koh
l,&
F.R
uker
.N
ucle
otid
ese
-qu
ence
ofth
ecD
NA
enco
ding
the
V-r
egio
nsof
the
H-a
ndL-
chai
nsof
ahu
-m
anm
onoc
lona
lant
ibod
ysp
ecifi
cto
HIV
-1gp
41.
Nu
clA
cid
sR
es1
8:49
27,
1990
.(M
edlin
e:90
3704
90).
[Fer
ns(1
989)
]R
.B
.F
erns
,J.
C.
Par
trid
ge,
R.
P.S
penc
e,N
.H
unt,
&R
.S
.Te
dder
.E
pito
pelo
catio
nof
13an
ti-ga
gH
IV-1
mon
oclo
nala
ntib
odie
sus
ing
olig
opep
tides
and
thei
rcro
ss-r
eact
ivity
with
HIV
-2.
AID
S3:
829–
834,
1989
.(M
edlin
e:90
2116
79).
[Fer
ns(1
991)
]R
.B.F
erns
,J.C
.Par
trid
ge,M
.Tis
dale
,N.H
unt,
&R
.S.T
edde
r.M
onoc
lona
lant
ibod
ies
defin
elin
ear
and
conf
orm
atio
nale
pito
pes
ofH
IV-1
polg
ene
prod
ucts
.AID
SR
es
Hu
mR
etr
oviru
ses7:30
7–31
3,19
91.(
Med
line:
9129
1501
)N
otes
:21
anti-
RT
MA
bsw
ere
rais
edan
dch
arac
teriz
ed–
thre
ena
rrow
lyde
fined
linea
repi
tope
sw
ere
map
ped.
The
thre
elin
eara
ndse
lect
edco
nfor
mat
iona
lMA
bsar
ein
clud
edin
the
data
base
.
[Fer
ns(1
987)
]R
.B
.F
erns
,R
.S
.Te
dder
,&
R.
A.
Wei
ss.
Cha
ract
eriz
atio
nof
mon
oclo
nal
antib
odie
sag
ains
tth
ehu
man
imm
unod
efici
ency
viru
sga
gpr
oduc
tsan
dth
eir
use
inm
onito
ring
HIV
isol
ate
varia
tion.J
Ge
nV
irol
68:1
543–
1551
,198
7.(M
edlin
e:87
2248
02).
[Fev
rier
(199
5)]
M.
Fev
rier,
F.B
oude
t,A
.D
esla
ndre
s,&
J.T
heze
.Tw
one
whu
man
mon
oclo
nala
ntib
odie
sag
ains
tH
IVty
pe1
glyc
opro
tein
120:
char
-ac
teriz
atio
nan
dne
utra
lizin
gac
tiviti
esag
ains
tHIV
type
1st
rain
s.A
IDS
Re
sH
um
Re
trov
iru
ses1
1:49
1–50
0,19
95.
(Med
line:
9535
8909
).
[Fon
teno
t(19
95)]
J.D
.Fon
teno
t,T.
C.V
anC
ott,
B.S
.Par
ekh,
C.P
.Pau
,J.R
.G
eorg
e,D
.L.B
irx,S
.Zol
la-P
azne
r,M
.K.G
orny
,&J.
M.G
atew
ood.
Pre
sen-
tatio
nof
HIV
V3
loop
epito
pes
for
enha
nced
antig
enic
ity,i
mm
unog
enic
ityan
ddi
agno
stic
pote
ntia
l.AID
S9:
1121
–112
9,19
95.
(Med
line:
9609
8127
).
[For
thal
(199
5)]
D.
N.
For
thal
,G
.La
nduc
ci,
M.
K.
Gor
ny,
S.
Zol
la-P
azne
r,&
W.
E.
Rob
inso
n.F
unct
iona
lac
tiviti
esof
20hu
man
imm
unod
efici
ency
viru
sty
pe1
(HIV
-1)-
spec
ific
hum
anm
onoc
lona
lant
ibod
ies.
AID
SR
es
Hu
mR
etr
oviru
ses1
1:10
95–1
099,
1995
.(M
edlin
e:96
0892
16)
Not
es:A
serie
sof
test
sw
ere
perf
orm
edon
20hu
man
mon
oclo
nal
antib
odie
sto
asse
ssth
eir
pote
ntia
lth
erap
eutic
utili
ty.
Ant
ibod
ies
wer
ete
sted
for
pote
ntia
llyha
rm-
ful
com
plem
ent-
med
iate
dan
tibod
yen
hanc
ing
activ
ity(C
-AD
E),
and
for
pote
ntia
llybe
nefic
ialn
eutr
aliz
ing
activ
ityan
dan
tibod
yde
pend
ent
cellu
lar
cyto
toxi
city
AD
CC
.
[For
tin(2
000)
]J.
F.F
ortin
,R
.C
antin
,M
.G
.B
erge
ron,
&M
.J.
Tre
mbl
ay.
Inte
ract
ion
betw
een
virio
n-bo
und
host
inte
rcel
lula
radh
esio
nm
olec
ule-
1an
dth
ehi
gh-a
ffini
tyst
ate
ofly
mph
ocyt
efu
nctio
n-as
soci
ated
antig
en-1
onta
rget
cells
rend
ers
R5
and
X4
isol
ates
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
mor
ere
frac
tory
tone
utra
lizat
ion.V
irolo
gy
268:
493–
503,
2000
.(M
edlin
e:20
1718
50).
[Fou
ts(1
997)
]T.
R.
Fou
ts,
J.M
.B
inle
y,A
.T
rkol
a,J.
E.
Rob
inso
n,&
J.P.
Moo
re.
Neu
tral
izat
ion
ofth
ehu
man
imm
unod
efici
ency
viru
sty
pe1
pri-
mar
yis
olat
eJR
-FL
byhu
man
mon
oclo
nala
ntib
odie
sco
rrel
ates
with
anti-
body
bind
ing
toth
eol
igom
eric
form
ofth
een
velo
pegl
ycop
rote
inco
mpl
ex.
JV
irol7
1:27
79–2
785,
1997
.(M
edlin
e:97
2139
43)N
otes
:To
test
whe
ther
anti-
body
neut
raliz
atio
nof
HIV
-1pr
imar
yis
olat
esis
corr
elat
edw
ithth
eaf
finiti
es
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-14
DE
C20
00
for
the
olig
omer
icen
velo
pegl
ycop
rote
ins,
JRF
Lw
asus
edas
am
odel
pri-
mar
yvi
rus
and
apa
nelo
f13
hum
anM
Abs
wer
eev
alua
ted
for:
half-
max
imal
bind
ing
tore
cm
onom
eric
JRF
Lgp
120;
half-
max
imal
bind
ing
tool
igom
eric
-JR
FL
Env
expr
esse
don
the
surf
ace
oftr
ansf
ecte
d29
3ce
lls;
and
neut
ral-
izat
ion
ofJR
FL
ina
PB
MC
-bas
edne
utra
lizat
ion
assa
y.A
ntib
ody
affin
ityfo
rol
igom
eric
JRF
LE
nvbu
tnot
mon
omer
icJR
FL
gp12
0co
rrel
ated
with
JRF
Lne
utra
lizat
ion.
[Fou
ts(1
998)
]T.
R.
Fou
ts,
A.
Trk
ola,
M.
S.
Fun
g,&
J.P.
Moo
re.
Inte
rac-
tions
ofpo
lycl
onal
and
mon
oclo
nala
nti-g
lyco
prot
ein
120
antib
odie
sw
ithol
igom
eric
glyc
opro
tein
120-
glyc
opro
tein
41co
mpl
exes
ofa
prim
ary
HIV
type
1is
olat
e:re
latio
nshi
pto
neut
raliz
atio
n.AID
SR
es
Hu
mR
etr
oviru
ses
14:5
91–7
,19
98.
(Med
line:
9825
2387
)N
otes
:A
bre
activ
ityto
olig
omer
icfo
rms
ofgp
120
wer
eco
mpa
red
tone
utra
lizat
ion
ofth
em
acro
phag
etr
opic
prim
ary
viru
sJR
FL,
and
did
nota
lway
sco
rrel
ate.
Thi
sbu
ilds
upon
stud
ies
whi
chha
vesh
own
that
olig
omer
bind
ing
whi
lere
quire
dfo
rneu
tral
izat
ion,
isno
talw
ays
suffi
cien
t.M
Ab
205-
46-9
and
2G6
bind
olig
omer
with
high
affin
-ity
,co
mpa
rabl
eto
IgG
1b12
,bu
tun
like
IgG
1b12
,ca
nnot
neut
raliz
eJR
FL.
Fur
ther
mor
e,ne
utra
lizin
gan
dno
n-ne
utra
lizin
gse
rafr
omH
IV-1
infe
cted
peop
lear
esi
mila
rin
thei
rre
activ
ities
tool
igom
eric
JRF
LE
nvel
ope.
[Fra
nke
(199
2)]
L.F
rank
e,R
.G
runo
w,
R.
Mei
ssne
r,T.
Por
tsm
an,
&R
.vo
nB
aehr
.Inh
ibiti
onof
HIV
-1in
fect
ion
invi
tro
bym
urin
em
onoc
lona
lant
i-p24
antib
odie
s.J
Me
dV
irol3
7:13
7–14
2,19
92.
(Med
line:
9233
3288
).
[Fra
nkel
(199
8)]
S.
S.
Fra
nkel
,R
.M
.S
tein
man
,N
.L.
Mic
hael
,S
.R
.K
im,
N.B
hard
waj
,M.P
ope,
M.K
.Lou
der,
P.K
.Ehr
enbe
rg,P
.W.P
arre
n,D
.R.
Bur
ton,
H.K
atin
ger,
T.C
.Van
Cot
t,M
.L.R
obb,
D.L
.Birx
,&J.
R.M
asco
la.
Neu
tral
izin
gm
onoc
lona
lant
ibod
ies
bloc
khu
man
imm
unod
efici
ency
viru
sty
pe1
infe
ctio
nof
dend
ritic
cells
and
tran
smis
sion
toT
cells
.J
Viro
l72:
9788
–94
,199
8.(M
edlin
e:99
0308
86)
Not
es:I
nves
tigat
ion
ofth
ree
hum
anM
Abs
toel
icit
ane
utra
lizin
gef
fect
and
bloc
kH
IV-1
infe
ctio
nin
hum
ande
ndrit
icce
lls.
Pre
incu
batio
nw
ithN
Abs
IgG
1b12
ora
com
bina
tion
of2F
5/2G
12pr
even
ted
infe
ctio
nof
purifi
edD
Can
dtr
ansm
issi
onin
DC
/T-c
ellc
ultu
res.
[Fuj
ii(1
993)
]Y.
Fuj
ii,Y.
Nis
hino
,T.
Nak
aya,
K.
Toku
naga
,&
K.
Ikut
a.E
x-pr
essi
onof
hum
anim
mun
odefi
cien
cyvi
rus
type
1N
efan
tigen
onth
esu
rfac
eof
acut
ely
and
pers
iste
ntly
infe
cted
hum
anT-
cells
.V
acc
ine1
1:12
40,1
993.
(Med
line:
9407
8655
).
[Fuj
ii(1
996a
)]Y.
Fuj
ii,K
.O
take
,Y.
Fuj
ita,
N.
Yam
aim
oto,
Y.N
agai
,M
.Ta
shiro
,&
A.
Ada
chi.
Clu
ster
edlo
caliz
atio
nof
olig
omer
icN
efpr
o-
tein
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
onth
ece
llsu
rfac
e.F
EB
SL
ett
ers
395:
257–
261,
1996
a.(M
edlin
e:88
9810
7).
[Fuj
ii(1
996b
)]Y.
Fuj
ii,K
.Ota
ke,M
.Tas
hiro
,&A
.Ada
chi.
Hum
anim
mun
-od
efici
ency
type
1N
efpr
otei
non
the
cell
surf
ace
iscy
toci
dal
for
hum
anC
D4+
Tce
lls.F
EB
SL
ett
ers3
93:1
05–1
08,1
996b
.(M
edlin
e:96
3975
41).
[Fuj
ii(1
996c
)]Y.
Fuj
ii,K
.Ota
ke,M
.Tas
hiro
,&A
.Ada
chi.
Invi
tro
cyto
cida
lef
fect
sof
hum
anim
mun
odefi
cien
cyvi
rus
type
1N
efon
unpr
imed
hum
anC
D4+
Tce
llsw
ithou
tMH
Cre
stric
tion.J
Ge
nV
irol7
7:29
43–2
951,
1996
c.(M
edlin
e:90
0008
4).
[Fuj
ii(1
996d
)]Y.
Fuj
ii,K
.O
take
,M
.Ta
shiro
,&
A.
Ada
chi.
Sol
uble
Nef
antig
enof
HIV
-1is
cyto
toxi
cfo
rhum
anC
D4+
Tce
lls.
FE
BS
Le
tte
rs393
:93–
96,1
996d
.(M
edlin
e:88
0443
2).
[Fun
g(1
992)
]M
.S
.C
.F
ung,
C.
R.
Y.S
un,
W.
L.G
ordo
n,R
.-S
.Li
ou,
T.W
.C
hang
,W.N
.C.S
un,E
.S.D
aar,
&D
.D.H
o.Id
entifi
catio
nan
dch
arac
ter-
izat
ion
ofa
neut
raliz
atio
nsi
tew
ithin
the
seco
ndva
riabl
ere
gion
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
gp12
0.JV
irol6
6:84
8–85
6,19
92.
(Med
-lin
e:92
1141
88)
Not
es:
Two
anti-
enve
lope
V2
antib
odie
sw
ere
rais
edth
atne
utra
lize
viru
sin
eith
era
conf
orm
atio
nde
pend
ent(
G3-
136)
orco
nfor
ma-
tion
inde
pend
ent(
BAT
085)
man
ner.
G3-
136
has
dim
inis
hed
reac
tivity
with
degl
ycos
ylat
ion
orD
TT
redu
ced
gp12
0,an
dsC
D4
inhi
bits
bind
ing
ina
com
petit
ion
assa
y;B
AT08
5is
nots
ensi
tive
toth
ese
alte
ratio
nsin
gp12
0.
[Fun
g(1
990)
]M
.S.C
.Fun
g,C
.R.Y
.Sun
,R.S
.Lio
u,W
.Gor
don,
N.T
.Cha
ng,
T.-W
.Cha
ng,&
N.-
C.S
un.
Mon
oclo
nala
nti-i
diot
ypic
antib
ody
mim
icki
ngth
epr
inci
pal
neut
raliz
atio
nsi
tein
HIV
-1gp
120
indu
ces
HIV
-1ne
utra
liz-
ing
antib
odie
sin
rabb
its.J
Imm
un
ol1
45:2
199–
2206
,19
90.
(Med
line:
9037
5916
).
[Fun
g(1
987)
]M
.S
.C
.F
ung,
C.
R.
Y.S
un,
N.-
C.
Sun
,N
.T.
Cha
ng,
&T.
-W
.Cha
ng.
Mon
oclo
nala
ntib
odie
sth
atne
utra
lize
HIV
-1vi
rions
and
inhi
bit
sync
ytiu
mfo
rmat
ion
byin
fect
edce
lls.Bio
tech
no
log
y5:9
40–9
47,1
987.
[Gau
duin
(199
6)]
M.-
C.
Gau
duin
,G
.P.
Alla
way
,P.
J.M
addo
n,C
.F.
Bar
bas
III,D
.R.B
urto
n,&
R.A
.Kou
p.E
ffect
ive
Ex
Viv
oN
eutr
aliz
atio
nof
Hum
anIm
mun
odefi
cien
cyV
irus
Type
1in
Pla
sma
byR
ecom
bina
ntIm
mun
oglo
b-ul
inM
olec
ules
.JV
irol7
0:25
86–2
592,
1996
.(M
edlin
e:96
1839
10)
Not
es:
Viru
sdi
rect
from
plas
ma
from
six
HIV
-1in
fect
edin
divi
dual
sw
asus
edfo
rne
utra
lizat
ion
assa
y.M
Ab
19b
coul
dne
utra
lize
2/6
plas
ma
sam
ples
,w
hile
MA
bIg
G1b
12co
uld
neut
raliz
e5/
6pl
asm
asa
mpl
es.C
D4-
base
dm
olec
ules
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-15
DE
C20
00
wer
eal
sote
sted
:CD
4-Ig
G2
was
effe
ctiv
ein
the
itex
vivo
assa
y,bu
tsC
D4
was
not.
Thu
s,M
Abs
IgG
1b12
and
CD
4-Ig
G2
have
broa
dan
dpo
tent
itin
vitr
oan
dit
exvi
vone
utra
lizin
gac
tiviti
es.
[Gau
duin
(199
5)]
M.
C.
Gau
duin
,J.
T.S
afrit
,R
.W
eir,
M.
S.
Fun
g,&
R.
A.
Kou
p.P
re-
and
post
-exp
osur
epr
otec
tion
agai
nsth
uman
imm
unod
efici
ency
viru
sty
pe1
infe
ctio
nm
edia
ted
bya
mon
oclo
nal
antib
ody.JIn
fect
Dis
171:
1203
–120
9,19
95.
(Med
line:
9527
1056
)N
otes
:P
assi
vepr
otec
tion
agai
nst
HIV
-1LA
Iw
ithM
Ab
BAT
123
was
achi
eved
inS
CID
mic
ere
con-
stitu
ted
with
hum
anpe
riphe
ralb
lood
lym
phoc
ytes
(hu-
PB
L-S
CID
)BAT
123
issp
ecifi
cfo
rth
eV
3lo
opgp
120
ofH
IV-1
LAI.
Ani
mal
sw
ere
prot
ecte
dag
ains
tsu
bseq
uent
infe
ctio
nw
ithLA
Ist
rain
,bu
tno
tot
her
viru
sst
rain
s,w
hen
BAT
123
was
give
n1
hour
befo
revi
rus
inoc
ulat
ion,
orup
to4
hour
spo
st-e
xpos
ure.
No
ther
apeu
ticef
fect
was
obse
rved
whe
nB
AT12
3w
asad
-m
inis
tere
daf
ter
infe
ctio
nha
dbe
enes
tabl
ishe
d.
[Gau
duin
(199
8)]
M.
C.
Gau
duin
,R
.W
eir,
M.
S.
Fun
g,&
R.
A.
Kou
p.In
-vo
lvem
ent
ofth
eco
mpl
emen
tsy
stem
inan
tibod
y-m
edia
ted
post
-exp
osur
epr
otec
tion
agai
nst
hum
anim
mun
odefi
cien
cyvi
rus
type
1.A
IDS
Re
sH
um
Re
trov
iru
ses1
4:20
5–11
,199
8.(M
edlin
e:98
1508
74)
Not
es:P
ost-
expo
sure
pass
ive
tran
sfer
ofm
urin
eB
AT12
3ca
nco
nfer
prot
ectio
nto
hu-P
BL-
SC
IDm
ice
chal
leng
edw
ithH
IV-1
LAI,
and
the
mec
hani
smis
byco
mpl
emen
t-m
edia
ted
cyto
lysi
sor
viro
lysi
s.T
his
prot
ectio
nw
asno
tco
nfer
red
byC
GP
4743
9,a
BAT
123
chim
era
that
has
ahu
man
IgG
1F
cdo
mai
n,su
bstit
uted
inpl
ace
ofa
mur
ine
IgG 1
Fc
dom
ain,
sugg
estin
gth
atth
epr
otec
tion
ism
edia
ted
byco
mpl
emen
t.F
urth
erev
iden
cew
asth
atth
epr
otec
tive
abili
tyof
BAT
123
islo
stw
hen
mic
ew
ere
trea
ted
with
cobr
ave
nom
fact
or,
whi
chin
activ
ates
seru
mco
mpl
emen
t.Ig
G 1do
esno
tfix
com
plem
ent
effic
ient
ly,
soan
IgG
2
MA
bm
ight
perf
orm
bette
r.T
here
fore
,in
spite
ofth
epo
tent
ialf
oren
hanc
e-m
ent
inso
me
circ
umst
ance
s,in
this
circ
umst
ance
com
plem
ent
activ
atio
npr
ovid
eda
prot
ectiv
ead
vant
age.
[Gef
fin(1
998)
]R
.B
.G
effin
,G
.B
.S
cott,
M.
Mel
enw
ick,
C.
Hut
to,
S.
Lai,
L.J.
Boo
ts,
P.M
.M
cKen
na,
J.K
essl
er,
&A
.J.
Con
ley.
Ass
ocia
tion
ofan
tibod
yre
activ
ityto
ELD
KW
A,
agl
ycop
rote
in41
neut
raliz
atio
nep
itope
,w
ithdi
seas
epr
ogre
ssio
nin
child
ren
perin
atal
lyin
fect
edw
ithH
IVty
pe1.
AID
SR
es
Hu
mR
etr
oviru
ses14:5
79–9
0,19
98.
(Med
line:
9825
2386
).
[Ger
shon
i(19
93)]
J.M
.Ger
shon
i,G
.Den
isov
a,D
.Rav
iv,N
.I.S
mor
odin
sky,
&D
.Buy
aner
.H
IVbi
ndin
gto
itsre
cept
orcr
eate
ssp
ecifi
cep
itope
sfo
rth
eC
D4/
gp12
0co
mpl
ex.FA
SE
BJ7
:118
5–11
87,
1993
.(M
edlin
e:93
3876
19)
Not
es:M
Abs
gene
rate
dto
asC
D4-
gp12
0co
mpl
ex,a
ndth
epo
tent
ialu
sefu
l-ne
ssfo
rva
ccin
ede
sign
ofep
itope
ssp
ecifi
cally
inth
eco
mpl
exis
disc
usse
d.
[Ghi
ara
(199
7)]
J.B
.Ghi
ara,
D.C
.Fer
guso
n,A
.C.S
atte
rthw
ait,
H.J
.Dys
on,
&I.
A.
Wils
on.
Str
uctu
re-b
ased
desi
gnof
aco
nstr
aine
dpe
ptid
em
imic
ofth
eH
IV-1
V3
loop
neut
raliz
atio
nsi
te.JM
olB
iol2
66:3
1–9,
1997
.(M
edlin
e:97
2076
75).
[Ghi
ara
(199
3)]
J.B
.Ghi
ara,
E.A
.Stu
ra,R
.L.S
tanfi
eld,
A.T
.Pro
fy,&
I.A
.W
ilson
.C
ryst
alst
ruct
ure
ofth
epr
inci
paln
eutr
aliz
atio
nsi
teof
HIV
-1.
Sci
-e
nce
264:
82–8
5,19
93.
(Med
line:
9418
8714
)N
otes
:Cry
sals
truc
ture
ofV
3lo
oppe
ptid
esbo
und
toF
abs
59.1
and
50.1
was
dete
rmin
ed.T
heG
PG
RA
Fm
otif
form
sa
doub
letu
rn.
[Gira
ud(1
999)
]A
.G
iraud
,Y.
Ata
man
-Ona
l,N
.B
atta
il,N
.P
iga,
D.
Bra
nd,
B.
Man
dran
d,&
B.
Verr
ier.
Gen
erat
ion
ofm
onoc
lona
lan
tibod
ies
tona
-tiv
ehu
man
imm
unod
efici
ency
viru
sty
pe1
enve
lope
glyc
opro
tein
byim
mu-
niza
tion
ofm
ice
with
nake
dR
NA
[InP
roce
ssC
itatio
n].JV
irol
Me
tho
ds
79:7
5–84
,199
9.(M
edlin
e:99
2590
89).
[Gla
ser
&H
ausd
orf(
1996
)]R
.W.G
lase
r&G
.Hau
sdor
f.B
indi
ngki
netic
sof
anan
tibod
yag
ains
tHIV
p24
core
prot
ein
mea
sure
dw
ithre
al-t
ime
biom
olec
ular
inte
ract
ion
anal
ysis
sugg
esta
slow
conf
orm
atio
nalc
hang
ein
antig
enp2
4.J
Imm
un
olo
gic
alM
eth
od
s189:
1–14
,199
6.(M
edlin
e:96
1635
39)
Not
es:T
heM
Ab
CD
-4/1
and
p24
have
unus
ualb
ipha
sic
kine
tics
ofas
soci
atio
n.
[Gol
ding
(199
5)]
B.G
oldi
ng,J
.Inm
an,P
.Hig
het,
R.B
lack
burn
,J.M
anis
che-
witz
,N.B
lyve
is,R
.D.A
ngus
,&H
.Gol
ding
.B
ruce
llaab
ortu
sco
njug
ated
with
agp
120
orV
3lo
oppe
ptid
ede
rived
from
hum
anim
mun
odefi
cien
cyvi
rus
type
1in
duce
sne
utra
lizin
gan
ti-H
IVan
tibod
ies,
and
the
V3-
B.a
bort
usco
njug
ate
isef
fect
ive
even
afte
rC
D4+
T-ce
llde
plet
ion.JV
irol6
9:32
99–
3307
,199
5.(M
edlin
e:95
2644
17).
[Gor
don
&D
elw
art(
2000
)]C
.J.
Gor
don
&E
.L.
Del
war
t.G
enet
icdi
vers
ityof
prim
ary
HIV
-1is
olat
esan
dth
eirs
ensi
tivity
toan
tibod
y-m
edia
ted
neut
ral-
izat
ion.
Viro
log
y27
2:32
6–30
,200
0.(M
edlin
e:20
3347
96).
[Gor
ny(1
992)
]M
.K
.G
orny
,A
.J.
Con
ley,
S.
Kar
wow
ska,
A.
Buc
hbin
der,
J.-Y
.X
u,E
.A
.E
min
i,S
.K
oeni
g,&
S.
Zol
la-P
azne
r.N
eutr
aliz
atio
nof
dive
rse
hum
anim
mun
odefi
cien
cyvi
rus
type
1va
riant
sby
anan
ti-V
3hu
man
mon
oclo
nala
ntib
ody.J
Viro
l66:
7538
–754
2,19
92.
(Med
line:
9305
9712
).
[Gor
ny(1
989)
]M
.K
.G
orny
,V.
Gia
naka
kos,
S.
Sha
rpe,
&S
.Z
olla
-Paz
ner.
Gen
erat
ion
ofhu
man
mon
oclo
nala
ntib
odie
sto
hum
anim
mun
odefi
cien
cy
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-16
DE
C20
00
viru
s.P
roc
Na
tlA
cad
Sci
US
A86:
1624
–162
8,19
89.
(Med
line:
8916
0828
)N
otes
:T
his
pape
rde
scrib
edim
mor
taliz
atio
nof
B-c
ells
from
HIV
-1po
si-
tive
indi
vidu
als
with
Eps
tein
-Bar
rvi
rus,
topr
oduc
ese
ven
stab
lean
tibod
ypr
oduc
ing
cell
lines
.
[Gor
ny(1
998)
]M
.K
.G
orny
,J.
R.
Mas
cola
,Z
.R
.Is
rael
,T.
C.
VanC
ott,
C.
Will
iam
s,P.
Bal
fe,
C.
Hio
e,S
.B
rodi
ne,
S.
Bur
da,
&S
.Z
olla
-Paz
ner.
Ahu
man
mon
oclo
nala
ntib
ody
spec
ific
for
the
V3
loop
ofH
IVty
pe1
clad
eE
cros
s-re
acts
with
othe
rH
IVty
pe1
clad
es.
AID
SR
es
Hu
mR
etr
oviru
ses
14:2
13–2
1,19
98.
(Med
line:
9815
0875
).
[Gor
ny(1
994)
]M
.K.G
orny
,J.P
.Moo
re,A
.J.C
onle
y,S
.Kar
wow
ska,
J.S
o-dr
oski
,C.W
illia
ms,
S.B
urda
,L.J
.Boo
ts,&
S.Z
olla
-Paz
ner.
Hum
anan
ti-V
2m
onoc
lona
lant
ibod
yth
atne
utra
lizes
prim
ary
butn
otla
bora
tory
isol
ates
ofhu
man
imm
unod
efici
ency
viru
sty
pe1.J
Viro
l68:
8312
–832
0,19
94.
(Med
-lin
e:95
0560
63)
Not
es:D
etai
led
char
acte
rizat
ion
ofth
eM
Ab
697-
D.
[Gor
ny(2
000)
]M
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orny
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C.
VanC
ott,
C.
Will
iam
s,K
.R
eves
z,&
S.
Zol
la-P
azne
r.E
ffect
sof
olig
omer
izat
ion
onth
eep
itope
sof
the
hum
anim
mun
odefi
cien
cyvi
rus
type
1en
velo
pegl
ycop
rote
ins.
Viro
log
y26
7:22
0–8,
2000
.(M
edlin
e:20
1307
36).
[Gor
ny(1
997)
]M
.K
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orny
,T.
C.
VanC
ott
and
Cat
arin
aH
ioe,
Z.
R.
Isra
el,
N.
L.M
icha
el,
A.
J.C
onle
yan
dC
onst
ance
Will
iam
s,J.
A.
Kes
sler
IIan
dP
adm
asre
eC
higu
rupa
tian
dS
herr
iBur
daan
d,&
S.
Zol
la-P
azne
r.H
uman
Mon
oclo
nalA
ntib
odie
sto
the
V3
Loop
ofH
IV-1
With
Intr
a-an
dIn
terc
lade
Cro
ss-R
eact
ivity
.J.Im
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no
l.159
:511
4–51
22,1
997.
(Med
line:
9803
1769
).
[Gor
ny(1
991)
]M
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orny
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-Y.
Xu,
V.G
iana
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s,S
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arw
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ms,
H.
W.
She
ppar
d,C
.V.
Han
son,
&S
.Z
olla
-Paz
ner.
Pro
duc-
tion
ofsi
te-s
elec
ted
neut
raliz
ing
hum
anm
onoc
lona
lant
ibod
ies
agai
nst
the
third
varia
ble
dom
ain
ofth
ehu
man
imm
unod
efici
ency
viru
sty
pe1
enve
-lo
pegl
ycop
rote
in.P
roc
Na
tlA
cad
Sci
US
A88:
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–324
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line:
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[Gor
ny(1
993)
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olla
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ner.
Rep
erto
ireof
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raliz
ing
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onoc
lona
lant
ibod
ies
spec
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fort
heV
3do
mai
nof
HIV
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120.J
Imm
un
ol1
50:6
35–6
43,1
993.
(Med
line:
9312
3766
)N
otes
:Cha
ract
eriz
aton
of12
hum
anM
Abs
that
bind
and
neut
raliz
eth
eM
Nis
olat
ew
ith50
%ne
utra
lizat
ion.
Two
ofth
ese
anti-
bodi
esal
sobo
und
and
neut
raliz
edIII
B:4
47-5
2-D
and
694/
98-D
;all
othe
rsco
uld
notb
ind
HX
B2
pept
ides
.All
butt
wo,
418-
Dan
d41
2-D
coul
dbi
ndto
SF
2pe
ptid
es.
[Gor
ny&
Zol
la-P
azne
r(20
00)]
M.
K.
Gor
ny&
S.
Zol
la-P
azne
r.R
ecog
nitio
nby
hum
anm
onoc
lona
lan
tibod
ies
offr
eean
dco
mpl
exed
pept
ides
repr
e-se
ntin
gth
epr
efus
ogen
ican
dfu
soge
nic
form
sof
hum
anim
mun
odefi
cien
cyvi
rus
type
1gp
41[In
Pro
cess
Cita
tion]
.J
Viro
l74:
6186
–92,
2000
.(M
edlin
e:20
3050
15).
[Gos
ting
(198
7)]
L.H
.Gos
ting,
J.M
cClu
re,E
.S.D
icki
nson
,S.M
.Wat
anab
e,K
.S
hriv
er,
&L.
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dste
in.
Mon
oclo
nala
ntib
odie
sto
gp11
0an
dgp
41of
hum
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mun
odefi
cien
cyvi
rus.J
Clin
Mic
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iol2
5:84
5–84
8,19
87.
(Med
line:
8722
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[Gra
nt(2
000)
]M
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nt,F
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aill,
S.M
ulle
r,H
.Koh
ler,
&K
.Ros
enth
al.
The
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idio
typi
can
tibod
y1F
7se
lect
ivel
yin
hibi
tscy
toto
xic
Tce
llsac
tivat
edin
HIV
-1in
fect
ion.
Imm
un
olC
ell
Bio
l78:
20–7
,200
0.(M
edlin
e:20
1178
40).
[Gra
ssi(
1991
)]F.
Gra
ssi,
R.M
enev
eri,
M.G
ullb
erg,
L.Lo
palc
o,G
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ossi
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Lanz
a,C
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antis
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ratts
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S.B
utto
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inel
li,A
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retta
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.G.
Sic
card
i.H
uman
Imm
unod
efici
ency
Viru
sTy
pe1
gp12
0M
imic
sa
Hid
den
Mon
omor
phic
Epi
tope
Bor
neby
Cla
ssIM
ajor
His
toco
mpa
tibili
tyC
ompl
exH
eavy
Cha
ins.J
Exp
Me
d174
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62,1
991.
(Med
line:
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[Gre
enw
ay(1
994)
]A
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A.
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hee,
E.
Grg
acic
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ewis
h,A
.Luc
anto
ni,I
.Mac
read
ie,&
A.A
zad.
Nef
27,b
utno
tthe
Nef
25is
ofor
mof
hum
anim
mun
odefi
cien
cyvi
rus-
type
1pN
L4.3
dow
n-re
gula
tes
surf
ace
CD
4an
dIL
-2R
expr
essi
onin
perip
hera
lblo
odm
onon
ucle
arce
llsan
dtr
ansf
orm
edT
cells
.Viro
log
y19
8:24
5–25
6,19
94.
(Med
line:
9408
2455
).
[Grim
ison
&La
uren
ce(1
995)
]B
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ison
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ence
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mun
odom
inan
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itope
regi
ons
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reve
rse
tran
scrip
tase
:co
rrel
atio
nsw
ithH
IV-1
+se
rum
IgG
inhi
bito
ryto
poly
mer
ase
activ
ityan
dw
ithdi
seas
epr
ogre
ssio
n.J
AID
S9:
58–6
8,19
95.
(Med
line:
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7740
).
[Gro
vit-
Fer
bas
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0)]
K.
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vit-
Fer
bas,
J.F.
Hsu
,J.
Fer
bas,
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an,
&I.
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Che
n.E
nhan
ced
bind
ing
ofan
tibod
ies
tone
utra
lizat
ion
epito
pes
follo
win
gth
erm
alan
dch
emic
alin
activ
atio
nof
hum
anim
mun
odefi
cien
cyvi
rus
type
1[In
Pro
cess
Cita
tion]
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irol
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802–
9,20
00.
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line:
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4970
).
[Gru
now
(199
0)]
R.G
runo
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.Gie
ss,T
.Por
tsm
an,H
.Dop
el,K
.Han
sel,
&R
.vo
nB
aehr
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evel
opm
ent
and
biol
ogic
alte
stin
gof
hum
anan
dm
urin
ean
tibod
ies
agai
nstH
IVan
tigen
s.ZK
linM
ed
45:3
67–3
69,1
990.
[Gu
(199
6)]
Z.G
u,Z
.Li,
Y.Q
uan,
M.A
.Par
niak
,&M
.A.W
ainb
erg.
Stu
d-ie
sof
aN
eutr
aliz
ing
Mon
oclo
nal
Ant
ibod
yto
Hum
anIm
mun
odefi
cien
cy
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-17
DE
C20
00
Viru
sTy
pe1
Rev
erse
Tra
nscr
ipta
se:
Ant
agon
istic
and
Syn
ergi
stic
Effe
cts
inR
eact
ions
Per
form
edin
the
Pre
senc
eof
Nuc
leos
ide
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Non
nucl
eosi
deIn
hibi
tors
,Res
pect
ivel
y.JV
irol7
0:26
20–2
626,
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edlin
e:96
1839
16).
[Gui
llerm
(199
8)]
C.
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llerm
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ert-
Heb
man
n,U
.H
ibne
r,M
.H
irn,
&C
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aux.
An
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CD
4(C
DR
3-lo
op)m
onoc
lona
lant
ibod
yin
hibi
tshu
man
imm
unod
efici
ency
viru
sty
pe1
enve
lope
glyc
opro
tein
-indu
ced
apop
tosi
s.V
irolo
gy
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254–
63,1
998.
(Med
line:
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[Gun
thar
d(1
994)
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Gun
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d,P.
L.G
owla
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chup
bach
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P.G
rob,
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el,
D.
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Bra
un,
&R
.Lu
thy.
Aph
ase
I/IIA
clin
ical
stud
yw
itha
chim
eric
mou
se-h
uman
mon
oclo
nala
ntib
ody
toth
eV
3lo
opof
hum
anim
mun
odefi
cien
cyvi
rus
type
Igp1
20.J
InfD
is17
0:13
84–1
393,
1994
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edlin
e:95
0884
17).
[Haa
heim
(199
1)]
L.R
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aahe
im,
J.P.
Mas
kell,
P.M
asca
gni,
&A
.R
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oate
s.F
ine
mol
ecul
arsp
ecifi
city
oflin
ear
and
asse
mbl
edan
tibod
ybi
nd-
ing
site
sin
HIV
-1p2
4.S
can
dJ
Imm
un
ol34
:341
–350
,19
91.
(Med
line:
9135
2532
)N
otes
:S
even
mur
ine
MA
bsto
a10
4-m
erpe
ptid
esp
anni
ngre
sidu
es27
0-37
3of
p24
gag
wer
ege
nera
ted.
[Hau
gan
(199
5)]
I.R
.H
auga
n,B
.M
.N
ilsen
,S
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orla
nd,
L.O
lsen
,&
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E.
Hel
land
.C
hara
cter
izat
ion
ofth
eD
NA
-bin
ding
activ
ityof
HIV
-1in
tegr
ase
usin
ga
filte
rbi
ndin
gas
say.B
ioch
em
Bio
ph
ysR
es
Co
mm
un
217:
802–
810,
1995
.(M
edlin
e:96
1253
14).
[He
(199
2)]
X.
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He,
F.R
uker
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.C
asal
e,&
D.
C.
Car
ter.
Str
uctu
reof
ahu
man
mon
oclo
nala
ntib
ody
Fab
frag
men
taga
inst
gp41
ofhu
man
imm
un-
odefi
cien
cyvi
rus
type
1.P
roc
Na
tlA
cad
Sci
US
A89:
7154
–715
8,19
92.
(Med
line:
9235
7790
).
[Hen
ders
on&
Per
cipa
lle(1
997)
]B
.R.H
ende
rson
&P.
Per
cipa
lle.I
nter
actio
nsbe
twee
nH
IVR
evan
dnu
clea
rim
port
and
expo
rtfa
ctor
s:th
eR
evnu
clea
rlo
calis
atio
nsi
gnal
med
iate
ssp
ecifi
cbi
ndin
gto
hum
anim
port
in-b
eta.
JM
ol
Bio
l274
:693
–707
,199
7.(M
edlin
e:98
0706
09).
[Her
nand
ez(2
000)
]M
.H
erna
ndez
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Poz
o,I.
Gom
ez,
&A
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elch
or.
Chi
mer
icsy
nthe
ticpe
ptid
eas
antig
enfo
rim
mun
odia
gnos
isof
HIV
-1in
-fe
ctio
n[In
Pro
cess
Cita
tion]
.Bio
che
mB
iop
hys
Re
sC
om
mu
n27
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line:
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9237
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[Hifu
mi(
2000
)]E
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oto,
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Uda
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owan
dw
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S-2
anti-
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nits
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ireth
eab
ility
toca
taly
zede
com
posi
tion
ofth
eco
nser
ved
sequ
ence
ofgp
41of
HIV
-1[In
Pro
cess
Cita
tion]
.A
pp
lBio
che
mB
iote
chn
ol
83:2
09–1
9;di
scus
sion
219–
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97–3
13,2
000.
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line:
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[Hill
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7)]
C.M
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nutm
az,V
.N.K
ewal
ram
ani,
L.B
astia
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.Gor
ny,S
.Zol
la-P
azne
r,&
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.Litt
man
.Env
elop
egl
ycop
rote
ins
from
hum
anim
mun
odefi
cien
cyvi
rus
type
s1
and
2an
dsi
mia
nim
mun
odefi
cien
cyvi
rus
can
use
hum
anC
CR
5as
aco
rece
ptor
for
vira
lent
ryan
dm
ake
dire
ctC
D4-
depe
nden
tint
erac
tions
with
this
chem
okin
ere
cept
or.
JV
irol7
1:62
96–
6304
,199
7.(M
edlin
e:97
4046
34).
[Hin
kula
(199
4)]
J.H
inku
la,
G.
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illja
m,
S.
Nor
dlun
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Bro
liden
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Hol
mbe
rg,E
.Ola
usso
n-H
anss
on,J
.Alb
ert,
E.S
ands
trom
,&B
.Wah
ren.
Imm
unol
ogic
alan
dvi
rolo
gica
lint
erac
tion
inpa
tient
sre
ceiv
ing
pass
ive
im-
mun
othe
rapy
with
HIV
-1ne
utra
lizin
gm
onoc
lona
lant
ibod
ies.
JA
IDS
7:94
0–95
1,19
94.(
Med
line:
9432
8227
)Not
es:E
leve
nH
IV-1
infe
cted
patie
nts
inth
ela
test
ages
wer
etr
eate
dw
ithm
ouse
MA
bsth
atsh
owed
high
HIV
-1ne
utra
l-iz
atio
n.T
heam
ount
ofp2
4in
the
sera
ofpa
tient
sde
crea
sed
infiv
epa
tient
s,bu
trem
aine
dth
esa
me
orin
crea
sed
insi
xof
them
.The
leve
lofv
iralR
NA
inth
epl
asm
aof
patie
nts
decr
ease
din
four
,sho
wed
noch
ange
sin
anot
her
four
and
incr
ease
din
the
othe
rth
ree.
By
them
selv
es,
the
MA
bsdi
dno
tap
pear
tobe
effic
ient
enou
ghto
decr
ease
the
viru
sbu
rden
ina
perm
anen
tfo
rmin
late
-sta
geH
IVpa
tient
s.
[Hin
kula
(199
0)]
J.H
inku
la,
J.R
osen
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-A.
Sun
dqvi
st,
T.S
tigbr
and,
&B
.W
ahre
n.E
pito
pem
appi
ngof
the
HIV
-1ga
gre
gion
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mon
oclo
nal
antib
odie
s.M
olI
mm
un
ol2
7:39
5–40
3,19
90.
(Med
line:
9030
9760
)N
otes
:Lo
caliz
atio
nof
imm
unog
enic
dom
ains
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4,p1
7,an
dp1
5.
[Hio
e(1
997)
]C
.H
ioe,
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Bur
da,
P.C
higu
rupa
ti,S
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u,&
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Zol
la-P
azne
r.R
estin
gce
llne
utra
lizat
ion
assa
yfo
rH
IV-1
prim
ary
isol
ates
.M
eth
od
s:A
com
pa
nio
nto
Me
tho
ds
inE
nzy
mo
log
y12
:300
–5,1
997.
(Med
line:
9740
1512
)N
otes
:Ate
chni
que
isde
scrib
edfo
rdet
ectin
gth
eac
tivity
ofne
utra
lizin
gpo
ly-
clon
alor
MA
bsag
ains
tHIV
-1pr
imar
yis
olat
es,u
sing
unst
imul
ated
PB
MC
asth
eta
rget
cell.
[Hio
e(1
999)
]C
.E.H
ioe,
J.E
.Hild
reth
,&S
.Zol
la-P
azne
r.E
nhan
ced
HIV
type
1ne
utra
lizat
ion
byhu
man
anti-
glyc
opro
tein
120
mon
oclo
nala
ntib
odie
sin
the
pres
ence
ofm
onoc
lona
lan
tibod
ies
toly
mph
ocyt
efu
nctio
n-as
soci
ated
mol
ecul
e1.
AID
SR
es
Hu
mR
etr
oviru
ses15
:523
–31,
1999
.(M
edlin
e:99
2367
18).
[Hio
e(2
000)
]C
.E
.H
ioe,
G.
J.Jo
nes,
A.
D.
Ree
s,S
.R
atto
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,D
.B
irx,
C.M
unz,
M.K
.Gor
ny,M
.Tue
n,&
S.Z
olla
-Paz
ner.
Ant
i-CD
4-bi
ndin
gdo
-
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-18
DE
C20
00
mai
nan
tibod
ies
com
plex
edw
ithH
IVty
pe1
glyc
opro
tein
120
inhi
bitC
D4+
Tce
ll-pr
olife
rativ
ere
spon
ses
togl
ycop
rote
in12
0[In
Pro
cess
Cita
tion]
.A
IDS
Re
sH
um
Re
trov
iru
ses16
:893
–905
,200
0.(M
edlin
e:20
3318
70).
[Ho
(199
1a)]
D.D
.Ho,
M.S
.C.F
ung,
Y.C
ao,X
.L.L
i,C
.Sun
,T.W
.Cha
ng,
&N
.-C
.Sun
.A
noth
erdi
scon
tinuo
usep
itope
ongl
ycop
rote
ingp
120
that
isim
port
ant
inhu
man
imm
unod
efici
ency
viru
sty
pe1
neut
raliz
atio
nis
iden
-tifi
edby
am
onoc
lona
lant
ibod
y.Pro
cN
atl
Aca
dS
ciU
SA8
8:89
49–8
952,
1991
a.(M
edlin
e:92
0209
68)N
otes
:Ade
scrip
tion
ofth
ene
utra
lizin
gm
urin
eM
Ab
G3-
4.E
vide
nce
sugg
este
dth
atth
eG
3-4
epito
pew
asdi
scon
tinuo
us,
butl
ater
stud
ies
show
edm
argi
nalp
eptid
ebi
ndin
gin
the
V2
regi
on.
[Ho
(199
2)]
D.D
.Ho,
M.S
.C.F
ung,
H.Y
oshi
yam
a,Y.
Cao
,&J.
E.R
obin
son.
Dis
cont
inuo
usep
itope
son
gp12
0im
port
anti
nH
IV-1
neut
raliz
atio
n.A
IDS
Re
sH
um
Re
trov
iru
ses8:
1337
–133
9,19
92.
(Med
line:
9310
3804
)N
otes
:F
urth
erde
scrip
tion
ofth
ehu
man
MA
b15
ean
dth
em
urin
eM
Ab
G3-
4.gp
120
mut
ants
that
affe
ct15
eep
itope
bind
ing:
113,
257,
368,
370,
421,
427,
475;
four
ofth
ese
coin
cide
with
amin
oac
ids
impo
rtan
tfor
the
CD
4bi
ndin
gdo
mai
n.G
3-4
isne
utra
lizin
gan
dbe
have
slik
ea
disc
ontin
uous
epito
pe,a
ndpa
rtia
llybl
ocks
sCD
4bi
ndin
g.
[Ho
(199
1b)]
D.
D.
Ho,
J.A
.M
cKea
ting,
X.
L.Li
,T.
Mou
dgil,
E.
S.
Daa
r,N
.-C
.S
un,
&J.
E.
Rob
inso
n.C
onfo
rmat
iona
lepi
tope
ofgp
120
impo
rtan
tin
CD
4bi
ndin
gan
dhu
man
imm
unod
efici
ency
viru
sty
pe1
neut
raliz
atio
nid
entifi
edby
ahu
man
mon
oclo
nal
antib
ody.J
Viro
l65
:489
–493
,19
91b.
(Med
line:
9108
7324
)N
otes
:Ade
scrip
tion
ofth
ene
utra
lizin
ghu
man
MA
b15
e.It
bind
sto
HIV
-1w
itha
broa
dsp
ecifi
city
,an
dbl
ocks
gp12
0bi
ndin
gto
CD
4,an
dis
adi
scon
tinuo
usep
itope
;D
TT
redu
ctio
nof
env
abro
gate
sbi
ndin
g.
[Hoc
hlei
tner
(200
0a)]
E.
O.
Hoc
hlei
tner
,C
.B
orch
ers,
C.
Par
ker,
R.
J.B
ien-
stoc
k,&
K.
B.
Tom
er.
Cha
ract
eriz
atio
nof
adi
scon
tinuo
usep
itope
ofth
ehu
man
imm
unod
efici
ency
viru
s(H
IV)
core
prot
ein
p24
byep
itope
exci
sion
and
diffe
rent
ialc
hem
ical
mod
ifica
tion
follo
wed
bym
ass
spec
trom
etric
pep-
tide
map
ping
anal
ysis
.Pro
tein
Sci
9:48
7–96
,200
0a.
(Med
line:
2021
4275
).
[Hoc
hlei
tner
(200
0b)]
E.
O.
Hoc
hlei
tner
,M
.K
.G
orny
,S
.Z
olla
-Paz
ner,
&K
.B
.To
mer
.M
ass
spec
trom
etric
char
acte
rizat
ion
ofa
disc
ontin
uous
epi-
tope
ofth
eH
IVen
velo
pepr
otei
nH
IV-g
p120
reco
gniz
edby
the
hum
anm
onoc
lona
lant
ibod
y13
31A
.JIm
mu
no
l164
:415
6–61
,20
00b.
(Med
line:
2021
9252
).
[Hoh
ne(1
993)
]W
.E.H
ohne
,G.K
uttn
er,S
.Kie
ssig
,G.H
ousd
orf,
R.G
runo
w,
K.W
inkl
er,H
.Wes
sner
,E.G
iess
man
n,R
.Stie
ger,
J.S
chne
ider
-Mer
gene
r,R
.vo
nB
aehr
,&
D.
Sch
ombu
rg.
Str
uctu
ral
base
ofth
ein
tera
ctio
nof
am
onoc
lona
lan
tibod
yag
ains
tp2
4of
HIV
-1w
ithits
pept
ide
epito
pe.
Mo
lIm
mu
no
l30:
1213
–122
1,19
93.
(Med
line:
9401
9411
).
[Hua
ng(1
997)
]X
.Hua
ng,J
.J.B
arch
iJr,
F.D
.Lun
g,P.
P.R
olle
r,P.
L.N
ara,
J.M
usch
ik,&
R.R
.Gar
rity.
Gly
cosy
latio
naf
fect
sbo
thth
eth
ree-
dim
ensi
onal
stru
ctur
ean
dan
tibod
ybi
ndin
gpr
oper
ties
ofth
eH
IV-1
IIIB
GP
120
pept
ide.
Bio
che
mis
try3
6:10
846–
56,
1997
.(M
edlin
e:97
4541
33)
Not
es:
Gly
cosy
-la
ted
anal
ogue
sof
the
V3
loop
ofgp
120
wer
est
udie
dus
ing
NM
Ran
dci
rcul
ardi
chro
ism
spec
tros
copi
es,
and
byA
Bbi
ndin
gpr
oper
ties
toM
Ab
0.5β
.A24
-res
idue
pept
ide
from
the
HIV
-1III
Bis
olat
e(r
esid
ues
308-
331)
desi
gnat
edR
P13
5,w
asgl
ycos
ylat
edw
ithbo
thN
-an
dO
-lin
ked
suga
rs.
[Hun
t(19
90)]
J.C
.Hun
t,S
.M.D
esai
,J.M
.Cas
ey,T
.J.B
ollin
g,T.
K.L
eung
,R
.H.D
ecke
r,S
.G.D
evar
e,&
V.S
arin
.M
ouse
mon
oclo
nala
ntib
ody
5-21
-3
reco
gniz
esa
cont
iguo
us,c
onfo
rmat
ion-
depe
nden
tepi
tope
and
map
sto
ahy
drop
hilic
regi
onin
HIV
-1gp
41.A
IDS
Re
sH
um
Re
trov
iru
ses6:58
7–98
,19
90.
(Med
line:
9029
8075
).
[Inou
ye(1
998)
]P.
Inou
ye,E
.Che
rry,
M.H
su,S
.Zol
la-P
azne
r,&
M.A
.Wai
n-be
rg.
Neu
tral
izin
gan
tibod
ies
dire
cted
agai
nstt
heV
3lo
opse
lect
for
diffe
r-en
tes
cape
varia
nts
ina
viru
sw
ithm
utat
edre
vers
etr
ansc
ripta
se(M
184V
)th
anin
wild
-typ
ehu
man
imm
unod
efici
ency
viru
sty
pe1.AID
SR
es
Hu
mR
etr
oviru
ses1
4:73
5–40
,19
98.
(Med
line:
9830
5526
)N
otes
:T
heM
184V
subs
titut
ion
inR
Tyi
elds
high
leve
lres
ista
nce
to3T
Can
dlo
wle
velr
esis
-ta
nce
todd
Ian
ddd
C,
and
alte
rsth
epr
oper
ties
ofR
T.V
irus
cont
aini
ngth
ew
tfo
rmof
RT
grow
nin
the
pres
ence
ofth
eM
Ab
447-
Dde
velo
ps44
7-D
resi
stan
cein
36da
ys,
with
the
GP
GR
toG
PG
Ksu
bstit
utio
ns(A
GA
(R)
toA
AA
(K))
.447
-Dre
sist
ance
took
long
erto
acqu
irein
viru
sw
ithth
eM
184V
subs
titut
edR
T,an
dha
dth
efo
rmC
TR
PN
toC
TR
PY
(AA
C(N
)to
TAC
(Y))
atpo
sitio
n5
ofth
eV
3lo
op.
[Ishi
kaw
a(1
999)
]T.
Ishi
kaw
a,N
.O
kui,
N.
Kob
ayas
hi,
R.
Sak
uma,
T.K
i-ta
mur
a,&
Y.K
itam
ura.
Mon
oclo
nala
ntib
odie
sag
ains
tthe
min
imal
DN
A-
Bin
ding
dom
ain
inth
eca
rbox
y-te
rmin
alre
gion
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
Inte
gras
e.JV
irol7
3:44
75–8
0,19
99.
(Med
line:
9921
4393
).
[Jac
kson
(199
9)]
N.A
.Jac
kson
,M.L
evi,
B.W
ahre
n,&
N.J
.Dim
moc
k.P
rop-
ertie
san
dm
echa
nism
ofac
tion
ofa
17am
ino
acid
,V
3lo
op-s
peci
ficm
i-
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-19
DE
C20
00
croa
ntib
ody
that
bind
sto
and
neut
raliz
eshu
man
imm
unod
efici
ency
viru
sty
pe1
virio
ns.J
Ge
nV
irol8
0(
Pt1
):225
–36,
1999
.(M
edlin
e:99
1314
05).
[Jac
obso
n(19
98)]
J.M
.Ja
cobs
on.
Pas
sive
imm
uniz
atio
nfo
rth
etr
eatm
ent
ofH
IVin
fect
ion.
MtS
ina
iJM
ed6
5:22
–6,1
998.
(Med
line:
9812
0263
)Not
es:
Rev
iew
.
[Jag
odzi
nski
&T
rzec
iak(
2000
)]P.
P.Ja
godz
insk
i&W
.H
.T
rzec
iak.
App
li-ca
tion
ofm
onoc
lona
lant
ibod
ies
tom
onito
rth
esy
nthe
sis
ofa
glyc
opro
tein
core
ofen
velo
pegl
ycop
rote
ins
ofhu
man
imm
unod
efici
ency
viru
s(H
IV-1
).B
iom
ed
Ph
arm
aco
the
r54:5
0–3,
2000
.(M
edlin
e:20
1862
41).
[Jag
odzi
nski
(199
6)]
P.P.
Jago
dzin
ski,
J.W
ustn
er,
D.
Km
ieci
ak,
T.J.
Was
ik,
A.F
erta
la,A
.L.S
iero
n,M
.Tak
ahas
hi,T
.Tsu
ji,T.
Mim
ura,
M.S
.Fun
g,M
.K.
Gor
ny,M
.Klo
czew
iak,
Y.K
anek
o,&
D.K
ozbo
r.R
ole
ofth
eV
2,V
3,an
dC
D4-
bind
ing
dom
ains
ofG
P12
0in
curd
lan
sulfa
tene
utra
lizat
ion
sens
itivi
tyof
HIV
-1du
ring
infe
ctio
nof
Tly
mph
ocyt
es.Viro
log
y22
6:21
7–22
7,19
96.
(Med
line:
9712
4646
).
[Jan
vier
(199
0)]
B.
Janv
ier,
P.A
rchi
nard
,B
.M
andr
and,
A.
Gou
deau
,&
F.B
arin
.Li
near
B-c
ell
epito
pes
ofth
em
ajor
core
prot
ein
ofhu
man
im-
mun
odefi
cien
cyvi
rus
type
s1
and
2.JV
irol6
4:42
58–4
263,
1990
.(M
edlin
e:90
3478
19).
[Jan
vier
(199
2)]
B.
Janv
ier,
P.A
rchi
nard
,B
.M
andr
and,
A.
Gou
deau
,&
F.B
arin
.Li
near
B-c
ell
epito
pes
ofth
em
ajor
core
prot
ein
ofhu
man
im-
mun
odefi
cien
cyvi
rus
type
s1
and
2.(A
utho
r’sC
orre
ctio
n).
JV
irol6
6:61
3,19
92.
[Jan
vier
(199
6)]
B.
Janv
ier,
J.J.
Lasa
rte,
P.S
arob
e,J.
Hoe
beke
,A
.B
.-B
.F.
Bor
ras-
Cue
sta,
&F.
Bar
in.B
-cel
lepi
tope
sof
HIV
type
1p2
4ca
psid
prot
ein:
are
asse
ssm
ent.AID
SR
es
Hu
mR
etr
oviru
ses12:5
19–5
25,1
996.
(Med
line:
9629
6964
)N
otes
:T
here
activ
itypa
ttern
of45
over
lapp
ing
synt
hetic
pen-
tade
cape
ptid
es,
span
ning
amin
oac
ids
133
to36
3(p
24)
ofH
IV-1
p55
gag
prec
urso
r,us
ing
sera
from
20H
IV-1
posi
tive
and
8H
IVne
gativ
ein
divi
dual
sw
asde
term
ined
byE
LIS
A.A
pept
ide
cove
ring
aa17
8-19
2w
asre
cogn
ized
by40
%,a
nda
pept
ide
cove
ring
288-
302
ofp5
5by
45%
,ofH
IV-1
posi
tive
peop
le.A
pept
ide
cove
ring
aa27
2-32
2of
p55
was
reco
gniz
edby
mos
thum
anse
ra.
Aco
nfor
mat
iona
lepi
tope
invo
lvin
gse
quen
ces
from
aa18
3-18
6an
d28
9-29
2w
aspr
opos
ed,b
ased
byan
alog
yto
the
stru
ctur
eof
the
Men
govi
rus
VP
2pr
otei
n.
[Jef
fs(1
996)
]S
.A
.Je
ffs,
J.M
cKea
ting,
S.
Lew
is,
H.
Cra
ft,D
.B
iram
,P.
E.
Ste
phen
s,&
R.
L.B
rady
.A
ntig
enic
ityof
trun
cate
dfo
rms
ofth
ehu
man
imm
unod
efici
ency
viru
sty
pe1
enve
lope
glyc
opro
tein
.J
Ge
nV
irol7
7:14
03–
1410
,199
6.(M
edlin
e:96
3356
72).
[Jel
onek
(199
9)]
M.J
elon
ek,J
.Mas
krey
,K.S
teim
er,B
.Pot
ts,K
.Hig
gins
,&M
.K
ello
r.M
ater
nalm
onoc
lona
lant
ibod
yto
the
V3
loop
alte
rssp
ecifi
city
ofth
ere
spon
seto
ahu
man
imm
unod
efici
ency
viru
sva
ccin
e.J
Inf
Dis
174:
866–
9,19
99.
(Med
line:
9700
0089
).
[Jen
sen
(199
7)]
T.H
.Jen
sen,
A.J
ense
n,A
.M.S
zilv
ay,&
J.K
jem
s.P
robi
ngth
est
ruct
ure
ofH
IV-1
Rev
bypr
otei
nfo
otpr
intin
gof
mul
tiple
mon
oclo
nal
antib
ody-
bind
ing
site
s.F
EB
SL
ett4
14:5
0–4,
1997
.(M
edlin
e:97
4492
61)
Not
es:
Rev
was
map
ped
usin
gM
Ab
prot
ein
foot
prin
ting,
whi
chga
vere
-su
ltsth
atag
reed
wel
lwith
pept
ide
map
ping
,but
was
usef
ulfo
ride
ntify
ing
adi
scon
tinuo
usin
tera
ctio
nbe
twee
ntw
ore
gion
s.F
ootp
rints
supp
orte
da
pre-
viou
sly
prop
osed
stru
ctur
e(A
uer
eta
l.,B
ioch
emis
try,
33(1
994)
2988
-299
6)pr
edic
ting
that
ahe
lix-lo
op-h
elix
mot
ifin
Rev
brin
gsth
ete
rmin
ioft
hepr
o-te
inin
topr
oxim
ity.
[Jey
araj
ah(1
998)
]S
.Jey
araj
ah,C
.E.P
arke
r,M
.T.S
umm
er,&
K.B
.Tom
er.
Mat
rix-a
ssis
ted
lase
rde
sorp
tion
ioni
zatio
n/m
ass
spec
trom
etry
map
ping
ofhu
man
imm
unod
efici
ency
viru
s-gp
120
epito
pes
reco
gniz
edby
alim
ited
poly
clon
alan
tibod
y.J
Am
So
cM
ass
Sp
ect
rom9:
157–
65,1
998.
(Med
line:
9834
4538
).
[Jia
ng(1
998)
]S
.Ji
ang,
K.
Lin,
&M
.Lu
.A
conf
orm
atio
n-sp
ecifi
cm
ono-
clon
alan
tibod
yre
actin
gw
ithfu
sion
-act
ive
gp41
from
the
hum
anim
mun
-od
efici
ency
viru
sty
pe1
enve
lope
glyc
opro
tein
.J
Viro
l72:
1021
3–7,
1998
.(M
edlin
e:99
0309
35)
Not
es:
MA
bN
C-1
spec
ifica
llyre
cogn
izes
the
fuso
-ge
nic
core
ofgp
41,
whi
chal
low
sfo
ran
alys
isof
CD
4-in
duce
dco
nfor
ma-
tiona
lcha
nges
ingp
120
and
gp41
asw
ella
sid
entifi
catio
nof
med
iato
rsfo
rH
IV-1
fusi
on.
[Kal
land
(199
4a)]
K.H
.Kal
land
,A.M
Szi
lvay
,K.A
.Bro
ksta
d,W
.Sae
trev
ik,
&G
.H
auke
nes.
The
hum
anim
mun
odefi
cien
cyvi
rus
type
1R
evpr
otei
nsh
uttle
sbe
twee
nth
ecy
topl
asm
and
nucl
ear
com
part
men
ts.
Mo
lCe
llB
iol
14:7
436–
7444
,19
94a.
(Med
line:
9502
1273
)N
otes
:Te
nan
ti-N
efM
Abs
wer
ege
nera
ted
and
map
ped.
Nef
isex
pres
sed
intw
ois
omor
phic
form
s,an
dw
assh
own
tobe
expr
esse
dm
ainl
yin
the
Gol
gico
mpl
exan
dat
the
nucl
ear
mem
bran
e,bu
tocc
asio
nally
xin
the
nucl
eus,
part
icul
arly
inM
T-4
cells
.
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-20
DE
C20
00
[Kal
land
(199
4b)]
K.H
.Kal
land
,A.M
Szi
lvay
,E.L
angh
off,
&G
.Hau
kene
s.S
ubce
llula
rdi
strib
utio
nof
hum
anim
mun
odefi
cien
cyvi
rus
type
1R
evan
dco
loca
lizat
ion
ofR
evw
ithR
NA
splic
ing
fact
ors
ina
spec
kled
patte
rnin
the
nucl
eopl
asm
.JV
irol6
8:14
75–1
485,
1994
b.(M
edlin
e:94
1498
36).
[Kam
inch
ik(1
990)
]J.
Kam
inch
ik,N
.Bas
han,
D.P
inch
asi,
B.A
mit,
N.S
arve
r,M
.I.J
ohns
ton,
M.F
isch
er,Z
.Yav
inan
dM
Gor
ecki
,&A
.Pan
et.E
xpre
ssio
nan
dbi
oche
mic
alch
arac
teriz
atio
nof
hum
anim
mun
odefi
cien
cyvi
rus
type
1ne
fgen
epr
oduc
t.JV
irol6
4:34
47–3
454,
1990
.(M
edlin
e:90
2790
77).
[Kan
g(1
994)
]C
.-Y.
Kan
g,K
.Har
ihar
an,P
.L.N
ara,
J.S
odro
ski,
&J.
P.M
oore
.Im
mun
izat
ion
with
aso
lubl
eC
D4-
gp12
0co
mpl
expr
efer
entia
llyin
duce
sne
utra
lizin
gan
ti-hu
man
imm
unod
efici
ency
viru
sty
pe1
antib
odie
sdi
rect
edto
conf
orm
atio
n-de
pend
ente
pito
pes
ofgp
120.
JV
irol6
8:58
54–5
862,
1994
.(M
edlin
e:94
3351
02)N
otes
:Mos
toft
heM
Abs
gene
rate
din
this
stud
yw
ere
conf
orm
atio
nal,
butt
here
wer
efo
urth
atbo
und
aV
3lo
oppe
ptid
e.T
hese
four
coul
dne
utra
lize
lab
stra
ins
with
diffe
rent
effic
ienc
ies.
The
seM
Abs
wer
eve
ryse
nsiti
veto
subs
titut
ions
inth
eV
3lo
op,b
utal
soto
subs
titut
ions
inth
eba
seof
the
V1/
V2
loop
stru
ctur
e(1
20/1
21V
K/L
E),
indi
catin
gan
unde
rlyin
gco
nfor
mat
iona
lcha
ract
er.A
dditi
onal
ly,m
any
anti-
CD
4bi
ndin
gsi
teM
Abs
wer
ede
scrib
ed,t
hats
hare
da
sens
itivi
tyto
subs
titut
ions
atre
sidu
es36
8an
d37
0.A
noth
ercl
ass
ofM
Abs
was
foun
dth
atap
pear
edto
beco
nfor
mat
iona
llyse
nsiti
ve,a
ndsh
ared
are
duct
ion
inbi
ndin
gw
ithth
eam
ino
acid
subs
titut
ion
88N
/Pin
the
C1
dom
ain.
[Kar
wow
ska
(199
2a)]
S.
Kar
wow
ska,
M.
K.
Gor
ny,
A.
Buc
hbin
der,
V.G
i-an
akak
os,C
.Will
iam
s,T.
Fue
rst,
&S
.Zol
la-P
azne
r.P
rodu
ctio
nof
hum
anm
onoc
lona
lant
ibod
ies
spec
ific
for
conf
orm
atio
nala
ndlin
ear
non-
V3
epi-
tope
sof
gp12
0.AID
SR
es
Hu
mR
etr
oviru
ses8:10
99–1
106,
1992
a.(M
edlin
e:92
3687
27)N
otes
:Asi
ngle
linea
rMA
bw
asge
nera
ted,
toth
eim
mun
odom
i-na
ntdo
mai
nin
the
C-t
erm
inal
port
ion
ofgp
120.
Thi
san
tibod
ydi
dno
tinh
ibit
rCD
4-rg
p120
bind
ing
orne
utra
lize
IIIB
orM
N.T
hree
conf
orm
atio
nale
pi-
tope
bind
ing
MA
bsw
ere
also
desc
ribed
inth
ispa
per
that
coul
dne
utra
lize
IIIB
and
MN
.
[Kar
wow
ska
(199
2b)]
S.K
arw
owsk
a,M
.K.G
orny
,A.B
uchb
inde
r,&
S.Z
olla
-P
azne
r.Ty
pe-s
peci
fichu
man
mon
oclo
nal
antib
odie
scr
oss-
reac
tw
ithth
eV
3-lo
opof
vario
usH
IV-1
isol
ates
.Va
ccin
es
92p
ages
171–
174,
1992
b.N
otes
:Edi
tors
:F.B
row
n,H
.S.G
insb
erg
and
R.L
erne
r,C
old
Spr
ing
Har
bor
Labo
rato
ryP
ress
,Col
dS
prin
gH
arbo
r,N
Y.
[Kar
wow
ska
(199
3)]
S.
Kar
wow
ska,
M.
K.
Gor
ny,
S.
Cul
pepp
er,
S.
Bur
da,
S.
Laal
,K
.S
aman
ich,
&S
.Z
olla
-Paz
ner.
The
sim
ilarit
ies
and
dive
rsity
amon
ghu
man
mon
oclo
nala
ntib
odie
sto
the
CD
4-bi
ndin
gdo
mai
nof
HIV
-1.
Va
ccin
es
93p
ages
229–
232,
1993
.N
otes
:E
dito
rs:
F.B
row
n,H
.G
insb
erg
and
R.
Lern
er,
Col
dS
prin
gH
arbo
rLa
bora
tory
Pre
ss,
Col
dS
prin
gH
arbo
r,N
Y.44
7-D
was
the
mos
tbro
adly
cros
s-re
activ
ean
ti-V
3hu
man
MA
bte
sted
.
[Kau
l(19
99)]
R.
Kau
l,D
.T
raba
ttoni
,J.
Bw
ayo,
D.
Arie
nti,
A.
Zag
liani
,F.
Mw
angi
,C.K
ariu
ki,E
.Ngu
gi,K
.Mac
Don
ald,
T.B
lake
Bal
l,M
.Cle
rici,
&F.
Plu
mm
er.
HIV
-1-s
peci
ficm
ucos
alIg
Ain
aco
hort
ofH
IV-1
resi
stan
tK
enya
nse
xw
orke
rs.AID
S13
:23–
29,1
999.
(Med
line:
9922
3948
).
[Kel
ler
&A
rora
(199
9)]
M.
Kel
ler
&Y.
Aro
ra.
Inhi
bitio
nof
anti-
V3
loop
re-
spon
seto
are
com
bina
ntgp
120
SF
2va
ccin
ebe
pree
xist
ing
mon
oclo
nalA
b.A
IDS
Re
sa
nd
Hu
ma
nR
etr
oviru
ses
15:8
55–6
0,19
99.(
Med
line:
9930
8904
).
[Kel
ler
(199
3)]
P.M
.K
elle
r,B
.A
.A
rnol
d,A
.R
.S
haw
,R
.L.
Tolm
an,
F.Va
nM
iddl
esw
orth
,S.B
ondy
,V.K
.Rus
ieck
i,S
.Koe
nig,
S.Z
olla
-Paz
ner,
P.C
onar
d,E
.A
.E
min
i,&
A.
J.C
onle
y.Id
entifi
catio
nof
HIV
vacc
ine
cand
idat
epe
ptid
esby
scre
enin
gra
ndom
phag
eep
itope
libra
ries.
Viro
log
y19
3:70
9–71
6,19
93.
(Med
line:
9321
2503
)N
otes
:Alib
rary
of15
mer
sw
assc
reen
edfo
rre
activ
ityw
ith44
7-52
D.1
00s
of15
mer
sre
acte
d,of
whi
ch70
wer
ese
quen
ced.
All
buto
neco
ntai
ned
the
mot
ifG
PX
R.
[Kes
sler
(199
5)]
J.A
.Kes
sler
,P.M
.McK
enna
,E.A
.Em
ini,
&A
.J.C
onle
y.In
vitr
oas
sess
men
tof
the
ther
apeu
ticpo
tent
ialo
fan
ti-H
IV-1
mon
oclo
nal
neut
raliz
ing
antib
odie
s.Ge
nM
ee
tA
mS
oc
Mic
rob
iol95
:586
,T–
25,
1995
.N
otes
:Aid
slin
e:96
0506
22A
bstr
act.
[Kes
sler
II(1
997)
]J.
A.K
essl
erII,
P.M
.McK
enna
,E.A
.Em
ini,
C.P
.Cha
n,M
.D.P
atel
,S.K
.Gup
ta,G
.E.M
ark
III,C
.F.B
arba
sIII
,D.R
.Bur
ton,
&A
.J.
Con
ley.
Rec
ombi
nant
hum
anm
onoc
lona
lan
tibod
yIg
G1b
12ne
utra
lizes
dive
rse
hum
anim
mun
odefi
cien
cyvi
rus
type
1pr
imar
yis
olat
es.
AID
SR
es
Hu
mR
etr
oviru
ses1
3:57
5–82
,19
97.
(Med
line:
9728
1567
)N
otes
:A
nti-
CD
4bi
ndin
gdo
mai
nan
tibod
ies
gene
rally
dono
tneu
tral
ize
prim
ary
HIV
-1is
olat
es,w
ithth
eex
cept
ion
ofIg
G1b
12.M
any
prim
ary
isol
ates
wer
esh
own
tobe
neut
raliz
edby
IgG
1b12
,in
clud
ing
seve
raln
on-B
clad
ein
tern
atio
nal
isol
ates
.N
eutr
aliz
atio
nof
apr
imar
yis
olat
ew
ithM
Ab
IgG
1b12
did
not
requ
ireco
ntin
uous
expo
sure
toth
ean
tibod
y.A
com
plet
eIg
G1
mol
ecul
eof
ase
lect
edb1
2FA
bm
utan
twith
a>
400-
fold
incr
ease
inaf
finity
was
asse
mbl
edan
dev
alua
ted
inth
ein
fect
ivity
redu
ctio
nas
say
inco
mpa
rativ
est
udie
sw
ithth
epa
rent
IgG
1b12
antib
ody.
The
mut
antd
idno
tret
ain
the
leve
lofp
rimar
y
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-21
DE
C20
00
isol
ate
neut
raliz
atio
npo
tenc
yof
IgG
1b12
,des
pite
the
incr
ease
inaf
finity
for
gp12
0.
[Kho
uri(
1995
)]Y.
F.K
hour
i,K
.McI
ntos
h,L.
Cav
acin
i,M
.Pos
ner,
M.P
agan
o,R
.Tuo
mal
a,&
W.A
.Mar
asco
.Ve
rtic
alT
rans
mis
sion
ofH
IV-1
.Cor
rela
tion
with
mat
erna
lvira
lloa
dan
dpl
asm
ale
vels
ofC
D4
bind
ing
site
anti-
gp12
0an
tibod
ies.
JC
linIn
vest
95:7
32–7
37,
1995
.(M
edlin
e:95
1647
06)
Not
es:
Diff
eren
ces
inle
vels
ofA
bsdi
rect
edag
ains
tth
em
onom
eric
gp12
0an
dag
ains
tthe
V3
loop
regi
onof
gp12
0w
ere
nots
igni
fican
tlydi
ffere
ntbe
twee
ntr
ansm
ittin
gan
dno
n-tr
ansm
ittin
gm
othe
rs.D
iffer
ence
sw
ere
obse
rved
inth
ele
vels
ofC
D4
bind
ing
site
antib
odie
s,as
dete
rmin
edby
the
abili
tyof
dilu
ted
mat
erna
lpl
asm
ato
inhi
bit
bind
ing
ofth
eC
D4
bind
ing
site
mon
oclo
nal
antib
ody
F10
5(M
Ab
F10
5)to
mon
omer
icgp
120.
[Kim
(199
7)]
J.J.
Kim
,V.
Ayy
avoo
,M
.L.
Bag
araz
zi,
M.
Cha
tterg
oon,
J.D
.B
oyer
,B.W
ang,
&D
.B.W
eine
r.D
evel
opm
ento
fam
ultic
ompo
nent
can-
dida
teva
ccin
efo
rH
IV-1
.Va
ccin
e15:
879–
83,1
997.
(Med
line:
9737
8941
).
[Kin
ney
Tho
mas
(198
8)]
E.
Kin
ney
Tho
mas
,J.
N.
Web
er,
J.M
cClu
re,
P.R
.C
laph
am,M
.C.S
ingh
al,M
.K.S
hriv
er,&
R.A
.Wei
ss.
Neu
tral
izin
gm
on-
oclo
nal
antib
odie
sto
the
AID
Svi
rus.
AID
S2:
25–2
9,19
88.
(Med
line:
8819
2838
).
[Kita
mur
a(1
999)
]Y.
Kita
mur
a,T.
Ishi
kaw
a,N
.Oku
i,N
.Kob
ayas
hi,T
.Kan
da,
T.S
him
ada,
K.
Miy
ake,
&K
.Yo
shiik
e.In
hibi
tion
ofre
plic
atio
nof
HIV
-1at
both
early
and
late
stag
esof
the
vira
llife
cycl
eby
sing
le-c
hain
antib
ody
agai
nstv
irali
nteg
rase
.JA
cqu
irIm
mu
ne
De
ficS
ynd
rHu
mR
etr
oviro
l20
:105
–14
,199
9.(M
edlin
e:99
1399
18).
[Kla
sse
(199
3a)]
P.K
lass
e,J.
A.
McK
eatin
g,M
.S
chut
ten,
M.
S.
Rei
tz,
&M
.R
ober
t-G
urof
f.A
nim
mun
e-se
lect
edpo
int
mut
atio
nin
the
tran
smem
-br
ane
prot
ein
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
(HX
B2-
Env
:Ala
582(
–>T
hr))
decr
ease
svi
raln
eutr
aliz
atio
nby
mon
oclo
nala
ntib
odie
sto
the
CD
4-bi
ndin
gsi
te.V
irolo
gy
196:
332–
337,
1993
a.(M
edlin
e:93
3624
23).
[Kla
sse
(199
1)]
P.J.
Kla
sse,
R.P
ipko
rn,&
J.B
lom
berg
.A
clus
ter
ofco
ntin
u-ou
san
tigen
icst
ruct
ures
inth
etr
ansm
embr
ane
prot
ein
ofH
IV-1
:Ind
ivid
ual
patte
rns
ofre
activ
ityin
hum
anse
ra.
Mo
lIm
mu
no
l28:
613–
622,
1991
.(M
ed-
line:
9131
9155
).
[Kla
sse
(199
3b)]
P.J.
Kla
sse,
R.P
ipko
rn,J
.Blo
mbe
rg,K
.-Y.
Han
,B.H
ilton
,&
J.A
.F
erre
tti.
Thr
ee-d
imen
sion
alst
ruct
ure
and
antig
enic
ityof
tran
smem
bran
e-pr
otei
npe
ptid
esof
the
hum
anim
mun
odefi
cien
cyvi
rus
type
1.F
EB
SL
ett
ers3
23:6
8–72
,199
3b.
(Med
line:
9326
5946
).
[Kla
sse
&S
atte
ntau
(199
6)]
P.J.
Kla
sse
&Q
.J.S
atte
ntau
.A
ltere
dC
D4
inte
r-ac
tions
ofH
IVty
pe1
LAIv
aria
nts
sele
cted
fort
heca
paci
tyto
indu
cem
em-
bran
efu
sion
inth
epr
esen
ceof
am
onoc
lona
lant
ibod
yto
dom
ain
2of
CD
4.A
IDS
Re
sH
um
Re
trov
iru
ses12:1
015–
1021
,199
6.(M
edlin
e:96
4247
56).
[Kou
p(1
991)
]R
.A.K
oup,
J.E
.Rob
inso
n,Q
.V.N
guye
n,C
.A.P
ikor
a,B
.Bla
is,
A.R
oske
y,D
.Pan
ical
i,&
J.L.
Sul
livan
.A
ntib
ody-
depe
nden
tcel
l-med
iate
dcy
toto
xici
tydi
rect
edby
ahu
man
mon
oclo
nala
ntib
ody
reac
tive
with
gp12
0of
HIV
-1.
AID
S5:
1309
–131
4,19
91.
(Med
line:
9211
8257
).
[Kro
pelin
(199
8)]
M.K
rope
lin,C
.Sus
al,V
.Dan
iel,
&G
.Ope
lz.
Inhi
bitio
nof
HIV
-1rg
p120
bind
ing
toC
D4+
Tce
llsby
mon
oclo
nala
ntib
odie
sdi
rect
edag
ains
tthe
gp12
0C
1or
C4
regi
on.
Imm
un
olL
ett6
3:19
–25,
1998
.(M
edlin
e:98
3839
39).
[Kun
ert(
1998
)]R
.Kun
ert,
F.R
uker
,&H
.Kat
inge
r.M
olec
ular
char
acte
riza-
tion
offiv
ene
utra
lizin
gan
ti-H
IVty
pe1
antib
odie
s:id
entifi
catio
nof
non-
conv
entio
nal
Dse
gmen
tsin
the
hum
anm
onoc
lona
lan
tibod
ies
2G12
and
2F5.
AID
SR
es
Hu
mR
etr
oviru
ses14:1
115–
28,1
998.
(Med
line:
9840
7601
)N
otes
:Stu
dyid
entifi
esfiv
ehu
man
MA
bsw
hich
wer
eab
leto
netu
raliz
epr
i-m
ary
isol
ates
ofdi
ffere
ntcl
adesin
vitr
oan
dre
port
sth
enu
cleo
tide
and
amin
oac
idse
quen
ces
ofth
ehe
avy
and
light
chai
nV
segm
ents
ofth
ean
tibod
ies.
[Kun
ert(
2000
)]R
.K
uner
t,W
.S
tein
felln
er,
M.
Pur
tsch
er,
A.
Ass
adia
n,&
H.
Kat
inge
r.S
tabl
ere
com
bina
ntex
pres
sion
ofth
ean
tiH
IV-1
mon
oclo
nal
antib
ody
2F5
afte
rIg
G3/
IgG
1su
bcla
sssw
itch
inC
HO
cells
.B
iote
chn
ol
Bio
en
g67:
97–1
03,2
000.
(Med
line:
2005
0117
).
[Kus
k(1
992)
]P.
Kus
k,T.
H.
Bug
ge,
B.
O.
Lind
hard
t,E
.F.
Hul
gaar
d,&
K.H
olm
back
.M
appi
ngof
linea
rB
-cel
lepi
tope
son
the
maj
orco
repr
otei
np2
4of
hum
anim
mun
odefi
cien
cyvi
rus
type
1.AID
SR
es
Hu
mR
etr
oviru
ses
8:17
89–1
794,
1992
.(M
edlin
e:93
0904
61)
Not
es:
.T
heep
itope
for
MA
bF
5-2
was
foun
dto
bere
activ
ew
ithhu
man
sera
from
HIV
-1in
fect
edin
divi
d-ua
ls,
and
reac
tivity
toth
isep
itope
was
asso
ciat
edw
ithdi
seas
epr
ogre
ssio
nan
dlo
wC
D4
T-ce
llco
unts
.
[Kus
k(1
988)
]P.
Kus
k,K
.Ulri
ch,J
.Zeu
then
,&G
.Pal
lese
n.Im
mun
olog
ical
char
acte
rizat
ion
and
dete
ctio
nof
the
maj
orco
repr
otei
np2
4of
the
hum
anim
mun
odefi
cien
cyvi
rus
(HIV
)usi
ngm
onoc
lona
lant
ibod
ies.
JA
IDS
1:32
6–33
2,19
88.
(Med
line:
8911
0736
).
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-22
DE
C20
00
[Kut
tner
(199
2)]
G.
Kut
tner
,E
.G
iess
man
n,B
.N
iem
ann,
K.
Win
kler
,R
.Gru
now
,J.H
inku
la,J
.Ros
en,B
.Wah
ren,
&R
.von
Bae
hr.I
mm
unog
lobu
-lin
Vre
gion
san
dep
itope
map
ping
ofa
mur
ine
mon
oclo
nala
ntib
ody
agai
nst
p24
core
prot
ein
ofH
IV-1
.Mo
lIm
mu
no
l29:
561–
564,
1992
.(M
edlin
e:92
2279
56)
Not
es:
The
nucl
eotid
ese
quen
ceof
the
VD
JH
and
VJ L
regi
ons
ofa
mur
ine
MA
b(C
B-m
ab-p
24/1
3-5)
agai
nstp
24w
asob
tain
ed.
[Kw
ong
(199
8)]
P.D
.Kw
ong,
R.W
yatt,
J.R
obin
son,
R.W
.Sw
eet,
J.S
odro
ski,
&W
.A.H
endr
icks
on.
Str
uctu
reof
anH
IVgp
120
enve
lope
glyc
opro
tein
inco
mpl
exw
ithth
eC
D4
rece
ptor
and
ane
utra
lizin
ghu
man
antib
ody.
Na
ture
393:
648–
659,
1998
.(M
edlin
e:98
3033
79)N
otes
:Com
men
tin:
Nat
ure
1998
Jun
18;3
93(6
686)
:630
-1.
The
X-r
aycr
ysta
lst
ruct
ure
was
solv
edat
2.5
Are
solu
tion
ofH
IV-1
gp12
0co
reco
mpl
exed
with
hum
anC
D4
and
the
antig
en-
bind
ing
frag
men
tofa
neut
raliz
ing
antib
ody
that
bloc
ksch
emok
ine-
rece
ptor
bind
ing.
[Laa
l(19
94)]
S.L
aal,
S.B
urda
,M.K
.Gor
ny,S
.Kar
wow
ska,
A.B
uchb
inde
r,&
S.Z
olla
-Paz
ner.
Syn
ergi
stic
neut
raliz
atio
nof
hum
anim
mun
odefi
cien
cyvi
rus
type
1by
com
bina
tions
ofhu
man
mon
oclo
nal
antib
odie
s.JV
irol
68:4
001–
4008
,19
94.
(Med
line:
9424
674)
Not
es:
Ant
ibod
ies
toth
eC
-te
rmin
alpa
rtof
gp12
0an
dth
eV
3lo
opw
ere
show
nto
act
syne
rgis
tical
lyw
ithan
ti-C
D4
bind
ing
site
MA
bsin
term
sof
neut
raliz
atio
n.C
-ter
min
alan
-tib
odie
sdi
dno
tsyn
ergi
zeV
3lo
opM
Ab
neut
raliz
atio
n.
[LaC
asse
(199
8)]
R.
A.
LaC
asse
,K
.E
.F
ollis
,T.
Mou
dgil,
M.
Tra
hey,
J.M
.B
inle
y,V.
Pla
nelle
s,S
.Zol
la-P
azne
r,&
J.H
.Nun
berg
.Cor
ecep
toru
tiliz
atio
nby
hum
anim
mun
odefi
cien
cyvi
rus
type
1is
not
apr
imar
yde
term
inan
tof
neut
raliz
atio
nse
nsiti
vity
.JV
irol7
2:24
91–5
,19
98.
(Med
line:
9813
9151
)N
otes
:AT-
cell
line-
adap
ted
(TC
LA)
deriv
ativ
eof
SIp
rimar
yis
olat
e16
8Pac
quire
dth
eab
ility
toto
bene
utra
lized
byan
ti-V
3M
Abs
257-
D,2
68-D
and
50.1
.T
hepr
imar
yis
olat
eco
uld
use
eith
erC
CR
5or
CX
CR
4,an
dw
asno
tne
utra
lized
whe
nin
fect
ion
was
dire
cted
via
eith
erpa
thw
ay,
but
the
TC
LAde
rivat
ive
uses
CX
CR
4on
lyan
dis
neut
raliz
ed.T
hus
core
cept
orus
age
isno
tth
epr
imar
yde
term
inan
tofd
iffer
entia
lneu
tral
izat
ion
sens
itivi
tyin
prim
ary
vers
usT
CLA
stra
ins.
[Lai
sney
&S
tros
berg
(199
9)]
I.L.
Lais
ney
&A
.D.S
tros
berg
.Dua
lspe
cific
ityof
ahu
man
neut
raliz
ing
mon
oclo
nala
ntib
ody,
spec
ific
for
the
V3
loop
ofG
P12
0(H
IV-1
).Im
mu
no
lLe
tt67:
185–
92,1
999.
(Med
line:
9929
5799
).
[Lak
e(1
989)
]D
.Lak
e,T.
Sug
ano,
Y.M
atsu
mot
o,Y.
Mas
uho,
E.A
.Pet
erse
n,P.
Feo
rino,
&E
.M
.H
ersh
.A
Hyb
ridom
aP
rodu
cing
Hum
anM
onoc
lona
l
Ant
ibod
yS
peci
ficfo
rG
lyco
prot
ein
120k
Da
ofH
uman
Imm
unod
efici
ency
Viru
s(H
IV-1
).L
ifeS
cie
nce
s45:
iii–x
,198
9.(M
edlin
e:90
0430
18).
[Lak
e(1
992)
]D
.F.L
ake,
T.K
awam
ura,
T.To
miy
ama,
W.E
.Rob
inso
n,Y.
Mat
-su
mot
o,Y.
Mas
uho,
&E
.M
.H
ersh
.G
ener
atio
nan
dch
arac
teriz
atio
nof
ahu
man
mon
oclo
nala
ntib
ody
that
neut
raliz
esdi
vers
eH
IV-1
isol
ates
invi
tro.
AID
S6:
17–2
4,19
92.
(Med
line:
9218
1621
).
[Lam
an(1
992)
]J.
D.L
aman
,M.M
.Sch
elle
kens
,Y.H
.Aba
ciog
lu,G
.K.L
ewis
,M
.Ter
smet
te,R
.A.M
.Fou
chie
r,J.
P.M
.Lan
gedu
k,E
.Cla
asse
n,&
W.J
.A.
Boe
rsm
a.Va
riant
-spe
cific
mon
oclo
nala
ndgr
oup-
spec
ific
poly
clon
alhu
man
imm
unod
efici
ency
viru
sty
pe1
neut
raliz
ing
antib
odie
sra
ised
with
synt
hetic
pept
ides
from
the
gp12
0th
irdva
riabl
edo
mai
n.JV
irol6
6:18
23–1
831,
1992
.(M
edlin
e:92
3337
09).
[Lam
an(1
993)
]J.
D.
Lam
an,
M.
M.
Sch
elle
kens
,G
.K
.Le
wis
,J.
P.M
oore
,T.
J.M
atth
ews,
J.P.
M.
Lang
edijk
,R
.H
.M
eloe
n,W
.J.
A.
Boe
rsm
a,&
E.C
laas
sen.
AH
idde
nR
egio
nin
the
Thi
rdVa
riabl
eD
omai
nof
HIV
-1III
Bgp
120
Iden
tified
bya
Mon
oclo
nalA
ntib
ody.A
IDS
Re
sH
um
Re
trov
iru
ses
9:60
5–61
2,19
93.
(Med
line:
9337
8781
)N
otes
:Ape
ptid
e(F
VT
IGK
IGN
M-
RQ
AH
C)i
nduc
edM
Ab
bind
sto
the
carb
oxy-
term
inal
flank
ofth
eV
3-lo
op,
butt
heep
itope
ison
lyex
pose
don
gp12
0w
hen
itis
trea
ted
with
SD
S-D
TT.
[Lan
gedi
jk(1
991)
]J.
P.M
.Lan
gedi
jk,N
.K.T
.Bac
k,P.
J.D
urda
,J.G
ouds
mit,
&R
.H.M
eloe
n.N
eutr
aliz
ing
activ
ityof
anti-
pept
ide
antib
odie
sag
ains
tthe
prin
cipa
lneu
tral
izat
ion
dom
ain
ofhu
man
imm
unod
efici
ency
viru
sty
pe1.
JG
en
Viro
l72:
2519
–252
6,19
91.
(Med
line:
9201
3970
)N
otes
:MA
bsw
ere
rais
edag
ains
tR
IQR
GP
GR
AF
VT
IGK
byim
mun
izin
gm
ice.
Fin
est
ruct
ure
ofM
Ab
bind
ing
site
sw
asm
appe
dus
ing
peps
can.
Pre
serv
atio
nof
the
βtu
rnat
the
tipof
the
loop
was
criti
cal.
[Lan
gedi
jk(1
992)
]J.
P.M
.La
nged
ijk,
N.
K.
T.B
ack,
E.
Kin
ney-
Tho
mas
,C
.Bru
ck,M
.Fra
ncot
te,J
.Gou
dsm
it,&
R.H
.Mel
oen.
Com
paris
onan
dfin
em
appi
ngof
both
high
and
low
neut
raliz
ing
mon
oclo
nala
ntib
odie
sag
ains
tth
epr
inci
paln
eutr
aliz
atio
ndo
mai
nof
HIV
-1.Arc
hV
irol1
26:1
29–1
46,1
992.
(Med
line:
9239
8435
).
[Lan
gedi
jk(1
995)
]J.
P.M
.Lan
gedi
jk,G
.Zw
art,
J.G
ouds
mit,
&R
.H.M
eloe
n.F
ine
Spe
cific
ityof
antib
ody
reco
gniti
onm
aypr
edic
tam
ino
acid
subs
titut
ion
inth
eth
irdva
riabl
ere
gion
ofgp
120
durin
gH
IVTy
pe1
infe
ctio
n.AID
SR
es
Hu
mR
etr
oviru
ses11
:115
3–62
,19
95.
(Med
line:
9615
7202
)N
otes
:To
inve
stig
ate
how
HIV
-1es
cape
sfr
omre
cogn
ition
,a
pane
lof
V3
pept
ides
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-23
DE
C20
00
base
don
sequ
ence
sde
rived
from
6H
IV-1
posi
tive
indi
vidu
als
was
test
edfo
rre
activ
ityw
ithau
tolo
gous
sera
sam
pled
over
time.
The
V3
regi
onun
derg
oes
imm
une
esca
peth
roug
hm
utat
ion.
[Las
ky(1
987)
]L.
A.
Lask
y,G
.N
akam
ura,
D.
H.
Sm
ith,
C.
Fen
nie,
C.
Shi
-m
asak
i,E
.P
atze
r,P.
Ber
man
,T.
Gre
gory
,&
D.
J.C
apon
.D
elin
eatio
nof
aR
egio
nof
the
Hum
anIm
mun
odefi
cien
cyV
irus
Type
1gp
120
Gly
copr
o-te
inC
ritic
alfo
rIn
tera
ctio
nw
ithth
eC
D4
Rec
epto
r.Ce
ll50
:975
–985
,198
7.(M
edlin
e:87
3017
41).
[Lee
(199
5)]
C.-
N.
Lee,
J.R
obin
son,
G.
Maz
zara
,Y.
-L.
Che
ng,
M.
Ess
ex,
&T.
-H.L
ee.
Con
trib
utio
nof
hype
rvar
iabl
edo
mai
nsto
the
conf
orm
atio
nof
abr
oadl
yne
utra
lizin
ggl
ycop
rote
in12
0ep
itope
.A
IDS
Re
sH
um
Re
trov
iru
ses
11:7
77–7
81,
1995
.(M
edlin
e:96
0538
39)
Not
es:
Del
etio
nof
the
V4
orV
5do
mai
ns,
inco
ntra
stto
the
V1,
V2
and
V3
dom
ains
ofgp
120,
affe
ctth
ebr
oadl
yne
utra
lizin
gep
itope
reco
gniz
edby
1.5e
bydi
stur
bing
the
over
all
conf
orm
atio
nof
the
enve
lope
prot
ein.
[Lee
(199
7)]
S.
Lee,
K.
Ped
en,
D.
S.
Dim
itrov
,C
.C
.B
rode
r,J.
Man
isch
e-w
itz,G
.Den
isov
a,J.
M.G
ersh
oni,
&H
.Gol
ding
.E
nhan
cem
ento
fhum
anim
mun
odefi
cien
cyvi
rus
type
1en
velo
pe-m
edia
ted
fusi
onby
aC
D4-
gp12
0co
mpl
ex-s
peci
ficm
onoc
lona
lant
ibod
y.JV
irol7
1:60
37–4
3,19
97.(
Med
line:
9736
6665
).
[Leg
aste
lois
&D
esgr
ange
s(20
00)]
I.Le
gast
eloi
s&
C.
Des
gran
ges.
Des
ign
and
intr
acel
lula
rac
tivity
ofa
hum
ansi
ngle
-cha
inan
tibod
yto
hum
anim
-m
unod
efici
ency
viru
sty
pe1
cons
erve
dgp
41ep
itope
.J
Viro
l74
:571
2–5,
2000
.(M
edlin
e:20
2838
32).
[Les
car
(199
9)]
J.Le
scar
,J.B
rynd
a,P.
Rez
acov
a,R
.Sto
urac
ova,
M.M
.Rio
t-to
t,V.
Chi
tarr
a,M
.Fab
ry,M
.Hor
ejsi
,J.S
edla
cek,
&G
.A.B
entle
y.In
hibi
tion
ofth
eH
IV-1
and
HIV
-2pr
otea
ses
bya
mon
oclo
nala
ntib
ody.Pro
tein
Sci
8:26
86–9
6,19
99.
(Med
line:
2009
5845
).
[Les
car
(199
6)]
J.Le
scar
,R.S
tour
acov
a,M
.M.R
iotto
t,V.
Chi
tarr
a,J.
Bry
nda,
M.F
abry
,M.H
orej
si,J
.Sed
lace
k,&
G.A
.Ben
tley.
Pre
limin
ary
crys
tallo
-gr
aphi
cst
udie
sof
anan
ti-H
IV-1
prot
ease
antib
ody
whi
chin
hibi
tsen
zym
eac
tivity
.Pro
tein
Sci
5:96
6–96
8,19
96.
(Med
line:
9630
3819
).
[Les
car
(199
7)]
J.Le
scar
,R.S
tour
acov
a,M
.M.R
iotto
t,V.
Chi
tarr
a,J.
Bry
nda,
M.
Fab
ry,
M.
Hor
ejsi
,J.
Sed
lace
k,&
G.
A.
Ben
tley.
Thr
ee-d
imen
sion
alst
ruct
ure
ofan
Fab
-pep
tide
com
plex
:str
uctu
ralb
asis
ofH
IV-1
prot
ease
inhi
-bi
tion
bya
mon
oclo
nala
ntib
ody.J
Mo
lBio
l267
:120
7–22
,199
7.(M
edlin
e:
9729
4651
)N
otes
:(G
enba
nk:
U62
632
U62
633)
F11
.2.3
2is
aM
Ab
rais
edag
ains
tH
IV-1
prot
ease
whi
chin
hibi
tspr
oteo
lytic
activ
ity.
The
stru
ctur
eof
the
com
plex
ofth
eF
abfr
agm
ent
and
the
synt
hetic
pept
ide
that
itbi
nds
to,
resi
dues
36to
46of
prot
ease
,ha
vebe
ende
term
ined
at2.
2A
Are
solu
tion,
and
that
ofth
eF
abin
the
free
stat
eha
sbe
ende
term
ined
at2.
6A
Are
solu
tion.
The
conf
orm
atio
nof
the
boun
dpe
ptid
esh
ows
noov
eral
lstr
uctu
rals
imila
rity
toth
eco
rres
pond
ing
segm
enti
nH
IV-1
prot
ease
.
[Lev
in(1
997)
]R
.Lev
in,A
.M.M
hash
ilkar
,T.D
orfm
an,A
.Buk
ovsk
y,C
.Zan
i,J.
Bag
ley,
J.H
inku
la,M
.Nie
drig
,J.A
lber
t,B
.Wah
ren,
H.G
.Got
tling
er,&
W.A
.Mar
asco
.In
hibi
tion
ofea
rlyan
dla
teev
ents
ofth
eH
IV-1
repl
icat
ion
cycl
eby
cyto
plas
mic
Fab
intr
abod
ies
agai
nst
the
mat
rixpr
otei
n,p1
7.M
ol
Me
d3:
96–1
10,1
997.
(Med
line:
9723
9591
).
[Lev
y-M
intz
(199
6)]
P.Le
vy-M
intz
,L.D
uan,
H.Z
hang
,B.H
u,G
.Dor
nadu
la,
M.
Zhu
,J.
Kul
kosk
y,D
.B
izub
-Ben
der,
A.
M.
Ska
lka,
&R
.J.
Pom
eran
tz.
Intr
acel
lula
rex
pres
sion
ofsi
ngle
-cha
inva
riabl
efr
agm
ents
toin
hibi
tea
rlyst
ages
ofth
evi
ral
life
cycl
eby
targ
etin
ghu
man
imm
unod
efici
ency
viru
sty
pe1
Inte
gras
e.JV
irol7
0:88
21–8
832,
1996
.(M
edlin
e:97
1260
87)
Not
es:
See
com
men
tsin
JV
irol1
998
Apr
;72(
4):3
505-
6.
[Lew
is(1
991)
]G
.Le
wis
,Y.
Aba
ciog
lu,
T.F
outs
,J.
Sam
son,
M.
Moo
rem
an,
G.
Bau
er,
R.
Tus
kan,
G.
Col
e,&
R.
Kam
in-L
ewis
.E
pito
pedo
min
ance
inth
ean
tibod
yre
spon
seto
reco
mbi
nant
gp16
0of
HIV
-IIIB
.V
acc
ine
s9
1pag
es15
7–16
3,19
91.
Not
es:E
dito
rs:F
.Bro
wn,
R.C
hano
ckan
dH
.S.G
insb
erg
and
R.
Lern
erC
old
Spr
ing
Har
bor
Labo
rato
ryP
ress
,C
old
Spr
ing
Har
bor,
NY.
[Li(
1997
)]A
.Li
,T.
W.
Bab
a,J.
Sod
rosk
i,S
.Z
olla
-Paz
ner,
M.
K.
Gor
ny,
J.R
obin
son,
M.
R.
Pos
ner,
H.
Kat
inge
r,C
.F.
Bar
bas
III,
D.
R.
Bur
ton,
T.-C
.C
hou,
&R
.M
Rup
rech
t.S
yner
gist
icne
utra
lizat
ion
ofa
chim
eric
SIV
/HIV
type
1vi
rus
with
com
bina
tions
ofhu
man
anti-
HIV
type
1en
velo
pem
onoc
lona
lant
ibod
ies
orhy
perim
mun
egl
obul
ins.AID
SR
es
an
dH
um
an
Re
trov
iru
ses1
3:64
7–65
6,19
97.
(Med
line:
9168
233)
Not
es:M
ultip
leco
m-
bina
tions
ofM
Abs
wer
ete
sted
for
thei
rab
ility
tosy
nerg
ize
neut
raliz
atio
nof
aS
HIV
cons
truc
tcon
tain
ing
HIV
IIIB
env.
All
ofth
eM
Ab
com
bina
tions
trie
dw
ere
syne
rgis
tic,s
ugge
stin
gsu
chco
mbi
natio
nsm
aybe
usef
ulfo
rpa
s-si
veim
mun
othe
rapy
orim
mun
opro
phyl
axis
.Bec
ause
SH
IVca
nre
plic
ate
inrh
esus
mac
aque
s,su
chap
proa
ches
can
pote
ntia
llybe
stud
ied
inan
itin
vivo
mon
key
mod
el.
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-24
DE
C20
00
[Li(
1998
)]A
.Li
,H
.K
atin
ger,
M.
R.
Pos
ner,
L.C
avac
ini,
S.
Zol
la-P
azne
r,M
.K
.G
orny
,J.
Sod
rosk
i,T.
C.
Cho
u,T.
W.
Bab
a,&
R.
M.
Rup
rech
t.S
yner
gist
icne
utra
lizat
ion
ofsi
mia
n-hu
man
imm
unod
efici
ency
viru
sS
HIV
-vp
u+by
trip
lean
dqu
adru
ple
com
bina
tions
ofhu
man
mon
oclo
nala
ntib
odie
san
dhi
gh-t
itera
nti-h
uman
imm
unod
efici
ency
viru
sty
pe1
imm
unog
lobu
lins.
JV
irol7
2:32
35–4
0,19
98.
(Med
line:
9818
4563
).
[Li(
1993
)]X
.Li,
E.A
man
doro
n,M
.A.W
ainb
erg,
&M
.A.P
arni
ak.
Gen
era-
tion
and
char
acte
rizat
ion
ofm
urin
em
onoc
lona
lant
ibod
ies
reac
tive
agai
nst
N-t
erm
inal
and
othe
rre
gion
sof
HIV
-1re
vers
etr
ansc
ripta
se.
JM
ed
Viro
l39
:251
–259
,199
3.(M
edlin
e:93
2249
19).
[Lia
o(2
000)
]M
.Lia
o,Y.
Lu,Y
.Xia
o,M
.P.D
ieric
h,&
Y.C
hen.
Indu
ctio
nof
high
leve
lofs
peci
fican
tibod
yre
spon
seto
the
neut
raliz
ing
epito
peE
LDK
WA
onH
IV-1
gp41
bype
ptid
e-va
ccin
e*[In
Pro
cess
Cita
tion]
.P
ep
tide
s21:
463–
8,20
00.
(Med
line:
2028
3864
).
[Lin
sley
(198
8)]
P.S
.Lin
sley
,J.A
.Led
bette
r,E
.Kin
ney-
Tho
mas
,&S
.-L.
Hu.
Effe
cts
ofA
nti-g
p120
Mon
oclo
nalA
ntib
odie
son
CD
4R
ecep
torB
indi
ngby
the
env
Pro
tein
ofH
uman
Imm
unod
efici
ency
Viru
sTy
pe1.
JV
irol6
2:36
95–
3702
,198
8.(M
edlin
e:88
3331
43).
[Lio
u(1
989)
]R
.S.L
iou,
E.M
.Ros
en,M
.S.C
.Fun
g,W
.N.C
.Sun
,C.S
un,
W.G
ordo
n,N
.T.C
hang
,&T.
W.C
hang
.Ach
imer
icm
ouse
-hum
anan
tibod
yth
atre
tain
ssp
ecifi
city
for
HIV
-1gp
120
and
med
iate
sth
ely
sis
ofth
eH
IV-
1-in
fect
edce
lls.J
Imm
un
ol1
43:3
967–
3975
,198
9.(M
edlin
e:90
0789
97).
[Litw
in(1
996)
]V.
Litw
in,K
.A.N
agas
him
a,A
.M.R
yder
,C.H
.Cha
ng,J
.M.
Car
ver,
W.C
.Ols
on,M
.Aliz
on,K
.W.H
asel
,P.J
.Mad
don,
&G
.P.A
llaw
ay.
Hum
anim
mun
odefi
cien
cyvi
rus
type
1m
embr
ane
fusi
onm
edia
ted
bya
labo
rato
ry-a
dapt
edst
rain
and
apr
imar
yis
olat
ean
alyz
edby
reso
nanc
een
ergy
tran
sfer
.JV
irol7
0:64
37–6
441,
1996
.(M
edlin
e:96
3231
71)
Not
es:F
usio
nof
prim
ary
(JR
FL)
and
TC
LA(L
AI)
stra
ins
ofth
evi
rus
wer
est
udie
d.T
hede
gree
,kin
etic
s,ne
utra
lpH
and
diva
lent
catio
nsre
quire
men
tsw
ere
sim
ilar
for
mem
bran
efu
sion
for
both
viru
ses.
How
ever
,th
ein
hibi
tion
offu
sion
bysC
D4
and
CD
4-Ig
G2
occu
rred
atvi
rus
neut
raliz
atio
nco
ncen
trat
ions
for
JRF
L,bu
thig
her
conc
entr
atio
nsw
ere
requ
ired
toin
hibi
tLA
Ifus
ion
than
tone
utra
lize
LAI,
sugg
estin
gth
atvi
raln
eutr
aliz
atio
nan
dfu
sion
-inhi
bitio
nar
edi
stin
ct.
[Liu
(199
5)]
X.L
iu,A
.Ota
,M.W
atan
abe,
S.U
eda,
A.S
aito
h,H
.Shi
naga
wa,
A.
Nak
ata,
T.K
urim
ura,
X.
Wan
g,Y.
Zha
o,&
etal
.T
hree
antig
enic
re-
gion
sin
p17
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
(HIV
-1)
reve
aled
by
mou
sem
onoc
lona
lant
ibod
ies
and
hum
anan
tibod
ies
inH
IV-1
carr
ier
sera
.M
icro
bio
lIm
mu
no
l39:
775–
85,1
995.
(Med
line:
9615
6439
).
[Llo
rent
e(1
999)
]M
.Ll
oren
te,
S.
San
chez
-Pal
omin
o,S
.M
anes
,P.
Luca
s,L.
Kre
mer
,I.
M.
De
Alb
oran
,J.
L.To
ran,
J.A
lcam
i,G
.D
elR
eal,
&M
.-A
.C
.N
atur
alhu
man
antib
odie
sre
trie
ved
byph
age
disp
lay
libra
ries
from
heal
thy
dono
rs:p
olyr
eact
ivity
and
reco
gniti
onof
hum
anim
mun
odefi
cien
cyvi
rus
type
1gp1
20ep
itope
s.Sca
nd
JIm
mu
no
l50:2
70–9
,19
99.
(Med
line:
9937
7229
).
[Loc
her
(199
9)]
C.
P.Lo
cher
,R
.M
.G
rant
,E
.A
.C
ollis
son,
G.
Rey
es-T
eran
,T.
Elb
eik,
J.O
.K
ahn,
&J.
A.
Levy
.A
ntib
ody
and
cellu
lar
imm
une
re-
spon
ses
inbr
eakt
hrou
ghin
fect
ion
subj
ects
afte
rH
IVty
pe1
glyc
opro
tein
120
vacc
inat
ion.
AID
SR
es
Hu
mR
etr
oviru
ses15:1
685–
9,19
99.
(Med
line:
2007
2107
).
[Loo
mis
-Pric
e(1
997)
]L.
D.
Loom
is-P
rice,
M.
Levi
,P.
R.
Bur
nett,
J.E
.va
nH
amon
t,R
.A.S
hafe
r,B
.Wah
ren,
&D
.L.B
irx.
Line
arep
itope
map
ping
ofhu
mor
alre
spon
ses
indu
ced
byva
ccin
atio
nw
ithre
com
bina
ntH
IV-1
Env
e-lo
pepr
otei
ngp
160.J
Ind
Mic
rob
iolB
iote
chn
ol19
:58–
65,1
997.
(Med
line:
9742
6676
).
[Lop
alco
(199
3)]
L.Lo
palc
o,R
.Lo
nghi
,F.
Cic
com
asco
lo,
A.
De
Ros
si,
M.P
elag
i,F.
And
roni
co,J
.P.M
oore
,B.T
.Sch
ulz,
A.B
eret
ta,&
A.G
.Sic
-ca
rdi.
Iden
tifica
tion
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
glyc
opro
tein
gp12
0/gp
41in
tera
ctin
gsi
tes
byth
eid
ioty
pic
mim
icry
oftw
om
onoc
lona
lan-
tibod
ies.
AID
SR
es
Hu
mR
etr
oviru
ses9:33
–39,
1993
.(M
edlin
e:93
1522
84)
Not
es:
The
MA
bM
38bi
nds
toth
eca
rbox
yte
rmin
usof
gp12
0,in
agp
41bi
ndin
gre
gion
.Thi
sM
Ab
was
used
tocr
eate
anan
ti-id
ioty
peM
Ab,
9G5A
,w
hich
can
bind
togp
41at
the
base
ofth
ecy
stei
nelo
op.T
hebi
ndin
gdo
mai
nsof
thes
etw
om
onoc
lona
lsar
eco
nsis
tent
with
the
C5
dom
ain
ofgp
120
bein
gab
leto
bind
toth
egp
41cy
stei
nelo
op.T
heM
Ab
M38
also
bind
sto
hum
anH
LAm
olec
ules
,in
antig
enic
hom
olog
yor
poss
ibly
mol
ecul
arm
imic
ry.
[Lu
(200
0a)]
Y.Lu
,Y.X
iao,
J.D
ing,
M.D
ieric
h,&
Y.H
.Che
n.Im
mun
ogen
ic-
ityof
neut
raliz
ing
epito
pes
onm
ultip
le-e
pito
peva
ccin
esag
ains
tHIV
-1.
Int
Arc
hA
llerg
yIm
mu
no
l121:
80–4
,200
0a.
(Med
line:
2015
3311
).
[Lu
(200
0b)]
Y.Lu
,Y.
Xia
o,J.
Din
g,M
.P.
Die
rich,
&Y.
H.
Che
n.M
ulti-
epito
peva
ccin
esin
tens
ivel
yin
crea
sed
leve
lsof
antib
odie
sre
cogn
izin
gth
ree
neut
raliz
ing
epito
pes
onhu
man
imm
unod
efici
ency
viru
s-1
enve
lope
prot
ein.
Sca
nd
JIm
mu
no
l51:4
97–5
01,2
000b
.(M
edlin
e:20
2534
66).
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-25
DE
C20
00
[Lun
din
(199
6)]
K.
Lund
in,
A.
Sam
uels
son,
M.
Jans
son,
J.H
inku
laJ,
B.
Wah
ren,
H.
Wig
zell,
&M
.A
.P
erss
on.
Pep
tides
isol
ated
from
rand
ompe
ptid
elib
rarie
son
phag
eel
icit
ane
utra
lizin
gan
ti-H
IV-1
resp
onse
:an
aly-
sis
ofim
mun
olog
ical
mim
icry
.Imm
un
olo
gy8
9:57
9–58
6,19
96.
(Med
line:
9014
825)
.
[Ly
&S
tam
atat
os(2
000)
]A
.Ly
&L.
Sta
mat
atos
.V
2lo
opgl
ycos
ylat
ion
ofth
ehu
man
imm
unod
efici
ency
viru
sty
pe1
SF
162
enve
lope
faci
litat
esin
ter-
actio
nof
this
prot
ein
with
CD
4an
dC
CR
5re
cept
ors
and
prot
ects
the
viru
sfr
omne
utra
lizat
ion
byan
ti-V
3lo
opan
dan
ti-C
D4
bind
ing
site
antib
odie
s[In
Pro
cess
Cita
tion]
.JV
irol7
4:67
69–7
6,20
00.
(Med
line:
2034
7338
).
[Mac
ieje
wsk
i(19
95)]
J.P.
Mac
ieje
wsk
i,F.
F.W
eich
old,
N.S
.You
ng,A
.Car
a,D
.Z
ella
,M
.S
.R
eitz
Jr,
&R
.C
.G
allo
.In
trac
ellu
lar
expr
essi
onof
an-
tibod
yfr
agm
ents
dire
cted
agai
nst
HIV
reve
rse
tran
scrip
tase
prev
ents
HIV
infe
ctio
nin
vitr
o.N
atM
ed1
:667
–673
,199
5.(M
edlin
e:96
0715
29)
Not
es:
Tra
nsdu
ctio
nof
gene
sth
aten
code
and
expr
ess
anti-
RT
Fab
inhi
bit
the
en-
zym
e,m
akin
gce
llsre
sist
antt
oH
IVin
fect
ion
bybl
ocki
ngan
early
stag
eof
vira
lrep
licat
ion.
The
auth
ors
prop
ose
that
iftr
ansd
uctio
nof
ave
ctor
into
lym
phoh
aem
atop
oiet
icst
emce
llsor
mat
ure
lym
phoc
ytes
beco
mes
feas
ible
,ge
netr
ansf
erth
erap
yha
spr
omis
efo
rtr
eatin
gA
IDS
.
[Mae
da(1
992)
]Y.
Mae
da,S
.Mat
sush
ita,T
.Hat
tori,
T.M
urak
ami,
&K
.Tak
at-
suki
.Cha
nges
inth
eR
eact
ivity
and
Neu
tral
izin
gA
ctiv
ityof
aTy
pe-S
peci
ficN
eutr
aliz
ing
Mon
oclo
nalA
ntib
ody
Indu
ced
byIn
tera
ctio
nof
Sol
uble
CD
4w
ithgp
120.
AID
SR
es
Hu
mR
etr
oviru
ses8:20
49–2
054,
1992
.(M
edlin
e:93
1522
78).
[Man
ca(1
995)
]F.
Man
ca,D
.Fen
oglio
,M.T
.Val
le,G
.L.P
ira,A
.Kun
kl,R
.S.
Bal
dera
s,R
.G
.B
acca
la,
D.
H.
Kon
o,A
.F
erra
ris,
D.
Sav
erin
o,F.
Lan-
cia,
L.Lo
zzi,
&A
.N
.T
heofi
lopo
ulos
.H
uman
The
lper
cells
spec
ific
for
HIV
reve
rse
tran
scrip
tase
:po
ssib
lero
lein
intr
astr
uctu
ralh
elp
for
HIV
enve
lope
-spe
cific
antib
odie
s.Eu
rJ
Imm
un
ol2
5:12
17–1
223,
1995
.(M
ed-
line:
9529
3014
).
[Man
i(19
94)]
J.-C
.Man
i,V.
Mar
chi,
&C
.Cuc
urou
.E
ffect
ofH
IV-1
pept
ide
pres
enta
tion
onth
eaf
finity
cons
tant
sof
two
mon
oclo
nala
ntib
odie
sde
ter-
min
edby
BIA
core
tech
nolo
gy.M
olI
mm
un
ol3
1:43
9–44
4,19
94.
(Med
line:
9423
9428
)N
otes
:Tw
oM
Abs
are
desc
ribed
;on
e41
-1di
dno
tre
quire
the
Cys
-Cys
disu
lfide
brid
gean
dlo
opfo
rmat
ion,
the
othe
r9-1
1de
pend
son
loop
form
atio
n.
[Mar
asco
(199
2)]
W.A
.Mar
asco
,J.B
agle
y,C
.Zan
i,M
.Pos
ner,
L.C
avac
ini,
W.A
.Has
eltin
e,&
J.S
odro
ski.
Cha
ract
eriz
atio
nof
the
cDN
Aof
aB
road
lyR
eact
ive
Neu
tral
izin
gH
uman
anti-
gp12
0M
onoc
lona
lA
ntib
ody.J
Clin
Inve
st90
:146
7–14
78,1
992.
(Med
line:
9301
6879
1).
[Mar
asco
(199
3)]
W.A
.Mar
asco
,W.A
.Has
eltin
e,&
S.Y
.Che
nS
Y.
Des
ign,
intr
acel
lula
rex
pres
sion
,an
dac
tivity
ofa
hum
anan
ti-hu
man
imm
unod
efi-
cien
cyvi
rus
type
1gp
120
sing
le-c
hain
antib
ody.Pro
cN
atl
Aca
dS
ciU
SA
90:7
889–
7893
,199
3.(M
edlin
e:93
3615
51)
Not
es:C
omm
enti
n:P
roc
Nat
lA
cad
Sci
US
A19
9390
:742
7-8.
[Mar
ks(1
992)
]J.
D.
Mar
ks,
B.
Wah
ren,
G.
Gill
jam
,J.
Hin
kula
,&
G.
Win
-te
r.C
loni
ngof
anH
IV-1
neut
raliz
ing
V3
spec
ific
mon
oclo
nala
ntib
ody
and
expr
essi
onas
am
ouse
-hum
anch
imae
rican
tigen
bind
ing
frag
men
tan
dan
-tib
ody.
JA
cqu
irIm
mu
ne
De
ficS
ynd
r1991
:116
2,19
92.
Not
es:
Aid
slin
e:11
1629
1Abs
trac
t:V
IIth
Inte
rnat
iona
lCon
fere
nce
onA
IDS
,Flo
renc
e,Ita
ly,
proc
eedi
ngs.
[Mar
oun
(199
9)]
R.G
.Mar
oun,
D.K
rebs
,M.R
osha
ni,H
.Por
umb,
C.A
ucla
ir,F.
Tro
alen
,&
S.
Fer
man
djia
n.C
onfo
rmat
iona
lasp
ects
ofH
IV-1
inte
gras
ein
hibi
tion
bya
pept
ide
deriv
edfr
omth
een
zym
ece
ntra
ldo
mai
nan
dby
antib
odie
sra
ised
agai
nst
this
pept
ide.Eu
rJ
Bio
che
m26
0:14
5–55
,19
99.
(Med
line:
9919
1694
).
[Mas
cola
(199
7)]
J.R
.M
asco
la,
M.
K.
Loud
er,
T.C
.Va
nCot
t,C
.V.
Sap
an,
J.S
.La
mbe
rt,
L.R
.M
uenz
,B
.B
unow
,D
.L.
Birx
,&
M.
L.R
obb.
Pot
ent
and
syne
rgis
ticne
utra
lizat
ion
ofhu
man
imm
unod
efici
ency
viru
s(H
IV)t
ype
1pr
imar
yis
olat
esby
hype
rimm
une
anti-
HIV
imm
unog
lobu
linco
mbi
ned
with
mon
oclo
nal
antib
odie
s2F
5an
d2G
12.JV
irol
71:7
198–
206,
1997
.(M
edlin
e:97
4564
78)
Not
es:
HIV
IGde
rived
from
the
plas
ma
ofH
IV-1
-in
fect
eddo
nors
,and
MA
bs2F
5an
d2G
12w
ere
test
edag
ains
tapa
nelo
f15
clad
eB
HIV
-1is
olat
es,u
sing
asi
ngle
conc
entr
atio
nth
atis
achi
evab
lein
vivo
(HIV
IG,2
,500
mic
rog/
ml;
MA
bs,2
5m
icro
g/m
l).W
hile
the
thre
ean
tibod
yre
agen
tsne
utra
lized
man
yof
the
viru
ses
test
ed,
pote
ncy
varie
d.T
hevi
rus
neut
raliz
atio
nac
hiev
edby
doub
leor
trip
leco
mbi
natio
nsw
asge
nera
llyeq
ual
toor
grea
ter
than
that
pred
icte
dby
the
effe
ctof
indi
vidu
alan
tibod
ies,
and
the
trip
leco
mbi
natio
nw
assh
own
tobe
syne
rgis
tican
dto
have
the
grea
test
brea
dth
and
pote
ncy.
Pas
sive
imm
unot
hera
pyfo
rtr
eatm
ent
orpr
ophy
laxi
sof
HIV
-1sh
ould
cons
ider
mix
ture
sof
thes
epo
tent
neut
raliz
ing
antib
ody
reag
ents
.
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-26
DE
C20
00
[Mat
suo
(199
2)]
K.
Mat
suo,
Y.N
ishi
no,
T.K
imur
a,R
.Y
amag
uchi
,A
.Y
a-m
azak
i,T.
Mik
ami,
&K
.Iku
ta.
Hig
hly
cons
erve
dep
itope
dom
ain
inm
ajor
core
prot
ein
p24
isst
ruct
ural
lysi
mila
ram
ong
hum
an,
sim
ian
and
felin
eim
mun
odefi
cien
cyvi
ruse
s.J
Ge
nV
irol7
3:24
45–2
450,
1992
.(M
edlin
e:93
0190
72)
Not
es:T
wo
MA
bsar
ede
scrib
edth
atbi
ndto
ahi
ghly
cons
erve
dre
gion
inp2
4,w
ithan
tigen
icco
nser
vatio
nbe
twee
nF
IV,S
IVan
dH
IV-1
.The
auth
ors
sugg
estt
his
mig
htbe
anim
mun
odom
inan
tdom
ain.
[Mat
sush
ita(1
992)
]S
.Mat
sush
ita,H
.Mae
da,K
.Kim
achi
,Y.E
da,Y
.Mae
da,
T.M
urak
ami,
S.
Toki
yosh
i,&
K.
Taka
tsuk
i.C
hara
cter
izat
ion
ofa
mou
se/h
uman
chim
eric
mon
oclo
nala
ntib
ody
(Cβ
1)to
apr
inci
paln
eutr
aliz
-in
gdo
mai
nof
the
hum
anim
mun
odefi
cien
cyvi
rus
type
1en
velo
pepr
otei
n.A
IDS
Re
sH
um
Re
trov
iru
ses8:11
07–1
115,
1992
.(M
edlin
e:92
3687
28).
[Mat
sush
ita(1
995)
]S
.M
atsu
shita
,S
.M
atsu
mi,
K.
Yosh
imur
a,T.
Mor
ikita
,T.
Mur
akam
i,&
K.T
akat
suki
.N
eutr
aliz
ing
mon
oclo
nala
ntib
odie
sag
ains
thu
man
imm
unod
efici
ency
viru
sty
pe2
gp12
0.JV
irol6
9:33
33–3
340,
1995
.(M
edlin
e:95
2644
21).
[Mat
sush
ita(1
988)
]S
.M
atsu
shita
,M
.R
ober
-Gur
off,
J.R
usch
e,A
.K
oito
,T.
Hat
tori,
H.
Hos
hino
,K
.Ja
vahe
rian,
K.
Taka
tsuk
i,&
S.
Put
ney.
Cha
r-ac
teriz
atio
nof
aH
uman
Imm
unod
efici
ency
Viru
sne
utra
lizin
gm
onoc
lona
lan
tibod
yan
dm
appi
ngth
ene
utra
lizin
gep
itope
.J
Viro
l62:
2107
–211
4,19
88.
(Med
line:
8821
5041
).
[McD
ouga
l(19
96)]
J.S
.M
cDou
gal,
M.
S.
Ken
nedy
,S
.L.
Orlo
ff,J.
K.
A.
Nic
hols
on,
&T.
J.S
pira
.M
echa
nism
sof
hum
anim
mun
odefi
cien
cyvi
rus
type
1(H
IV-1
)neu
tral
izat
ion:
Irre
vers
ible
inac
tivat
ion
ofin
fect
ivity
byan
ti-H
IV-1
antib
ody.
JV
irol7
0:52
36–5
245,
1996
.(M
edlin
e:96
3570
49)
Not
es:
Stu
dies
ofpo
lycl
onal
sera
auto
logo
usvi
rus
inac
tivat
ion
indi
cate
sth
atin
in-
divi
dual
sov
ertim
e,vi
ralp
opul
atio
nsem
erge
that
are
resi
stan
tto
inac
tivat
ing
effe
cts
ofea
rlier
sera
.
[McE
lrath
(200
0)]
M.
J.M
cElra
th,
L.C
orey
,D
.M
onte
fiori,
M.
Wol
ff,D
.Sch
war
tz,M
.Kee
fer,
R.B
elsh
e,B
.S.G
raha
m,T
.Mat
thew
s,P.
Wrig
ht,
G.
Gor
se,
R.
Dol
in,
P.B
erm
an,
D.
Fra
ncis
,A
.M
.D
ulie
ge,
D.
Bol
ogne
si,
D.
Sta
blei
n,N
.K
ette
r,&
P.F
ast.
Aph
ase
IIst
udy
oftw
oH
IVty
pe1
en-
velo
peva
ccin
es,c
ompa
ring
thei
rim
mun
ogen
icity
inpo
pula
tions
atris
kfo
rac
quiri
ngH
IVty
pe1
infe
ctio
n.A
IDS
Vacc
ine
Eva
luat
ion
Gro
up[In
Pro
-ce
ssC
itatio
n].A
IDS
Re
sH
um
Re
trov
iru
ses16
:907
–19,
2000
.(M
edlin
e:20
3318
71).
[McK
eatin
g(19
96)]
J.A
.McK
eatin
g.B
iolo
gica
lcon
sequ
ence
sof
hum
anim
-m
unod
efici
ency
viru
sty
pe1
enve
lope
poly
mor
phis
m:
does
varia
tion
mat
-te
r?19
95F
lem
ing
Lect
ure.J
Ge
nV
irol7
7:29
05–2
919,
1996
.(M
edlin
e:97
1524
98).
[McK
eatin
g(1
993a
)]J.
A.M
cKea
ting,
J.B
enne
tt,S
.Zol
la-P
azne
r,M
.Sch
ut-
ten,
S.
Ash
elfo
rd,
A.
Leig
h-B
row
n,&
P.B
alfe
.R
esis
tanc
eof
ahu
man
seru
m-s
elec
ted
hum
anim
mun
odefi
cien
cyvi
rus
type
1es
cape
mut
antt
one
u-tr
aliz
atio
nby
CD
4bi
ndin
gsi
tem
onoc
lona
lant
ibod
ies
isco
nfer
red
bya
sin-
gle
amin
oac
idch
ange
ingp
120.J
Viro
l67:
5216
–522
5,19
93a.
(Med
line:
9335
3595
).
[McK
eatin
g(1
992a
)]J.
A.
McK
eatin
g,J.
Cor
dell,
C.
J.D
ean,
&P.
Bal
fe.
Syn
ergi
stic
inte
ract
ion
betw
een
ligan
dsbi
ndin
gto
the
CD
4bi
ndin
gsi
tean
dV
3do
mai
nof
hum
anim
mun
odefi
cien
cyvi
rus
type
Igp
120.
Viro
log
y19
1:73
2–74
2,19
92a.
(Med
line:
9307
9876
).
[McK
eatin
g(1
992b
)]J.
A.M
cKea
ting,
J.P.
Moo
re,M
.Fer
guso
n,H
.S.M
ars-
den,
S.
Gra
ham
,J.
W.
Alm
ond,
D.
J.E
vans
,&
R.
A.
Wei
ss.
Mon
oclo
nal
antib
odie
sto
the
C4
regi
onof
hum
anim
mun
odefi
cien
cyvi
rus
type
1gp
120:
use
into
polo
gica
lana
lysi
sof
aC
D4
bind
ing
site
.A
IDS
Re
sH
um
Re
trov
iru
ses
8:45
1–45
9,19
92b.
(Med
line:
9228
7630
)N
otes
:Ant
ibod
ies
wer
ege
nera
ted
usin
gan
antig
enpo
liovi
rus
chim
era,
expr
essi
ngaa
430-
446
ofgp
120.
Re-
sults
sugg
est
that
WQ
EV
GK
AM
YAm
aybe
expo
sed
onth
esu
rfac
eof
rec
gp12
0.
[McK
eatin
g(1
993b
)]J.
A.
McK
eatin
g,C
.S
hotto
n,J.
Cor
dell,
S.
Gra
ham
,P.
Bal
fe,N
.Sul
livan
,M.C
harle
s,M
.Pag
e,A
.Bol
mst
edt,
S.O
lofs
son,
S.C
.K
aym
an,
Z.
Wu,
A.
Pin
ter,
C.
Dea
n,J.
Sod
rosk
i,&
R.
A.
Wei
ss.
Cha
rac-
teriz
atio
nof
neut
raliz
ing
mon
oclo
nala
ntib
odie
sto
linea
rand
conf
orm
atio
n-de
pend
ent
epito
pes
with
inth
efir
stan
dse
cond
varia
ble
dom
ains
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
gp12
0.JV
irol6
7:49
32–4
944,
1993
b.(M
ed-
line:
9332
3237
)N
otes
:Sub
stitu
tions
inth
eV
2lo
opca
nre
sult
inco
mpl
ete
diss
ocia
tion
ofgp
120
and
gp41
,su
gges
ting
alte
ratio
nsin
V2
can
affe
ctsu
buni
tas
sem
bly.
Oth
ersu
bstit
utio
nsal
low
edgp
120-
gp41
asso
ciat
ion
and
expr
essi
on,
but
inhi
bite
dvi
rale
ntry
orsy
ncyt
ia.
Bin
ding
ofso
me
neut
ral-
izin
gM
Abs
was
alte
red
byV
2su
bstit
utio
ns.
For
MA
bC
RA
-4,
chan
ges
atre
sidu
es19
1/19
2/19
3(Y
SL/
GS
S),
and
for
11/6
8b,
chan
ges
atre
sidu
es18
3/18
4(P
I/SG
),w
ithin
V2,
and
forb
oth
MA
bsa
posi
tion
435
(Y/H
)cha
nge
inC
4,ab
roga
tebi
ndin
g.T
hese
MA
bsca
nbi
ndto
V1
and
V2
dom
ains
inth
e
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-27
DE
C20
00
abse
nce
ofC
4do
mai
n,so
the
C4
subs
titut
ion
prob
ably
resu
ltsin
conf
orm
a-tio
nalc
hang
e.
[McK
eatin
g(1
992c
)]J.
A.
McK
eatin
g,M
.T
hali,
C.
Fur
man
,S
.K
arw
owsk
a,M
.K.G
orny
,J.C
orde
ll,S
.Zol
la-P
azne
r,J.
Sod
rosk
i,&
R.A
.Wei
ss.A
min
oac
idre
sidu
esof
the
hum
anim
mun
odefi
cien
cyvi
rus
type
1gp
120
criti
calf
orth
ebi
ndin
gof
rata
ndhu
man
neut
raliz
ing
antib
odie
sth
atbl
ock
the
gp12
0-sC
D4
inte
ract
ion.
Viro
log
y19
0:13
4–14
2,19
92c.
(Med
line:
9241
0588
).
[McK
eatin
g(1
996)
]J.
A.
McK
eatin
g,Y.
J.Z
hang
,C
.A
rnol
d,R
.F
rede
riks-
son,
E.
M.
Fen
yo,
&P.
Bal
fe.
Chi
mer
icvi
ruse
sex
pres
sing
prim
ary
enve
-lo
pegl
ycop
rote
ins
ofhu
man
imm
unod
efici
ency
viru
sty
peIs
how
incr
ease
dse
nsiti
vity
tone
utra
lizat
ion
byhu
man
sera
.V
irolo
gy
220:
450–
460,
1996
.(M
edlin
e:86
6139
5)N
otes
:Chi
mer
icvi
ruse
sfo
rHX
B2
with
prim
ary
isol
ate
gp12
0ga
vepa
ttern
sof
cell
trop
ism
and
cyto
path
icity
iden
tical
toth
eor
igi-
nalp
rimar
yvi
ruse
s.S
era
that
wer
eun
able
tone
utra
lize
the
prim
ary
isol
ates
wer
ein
som
eca
ses
able
tone
utra
lize
chim
eric
viru
ses,
indi
catin
gth
atso
me
ofth
ene
utra
lizin
gep
itope
sw
ere
ingp
41.
[McK
nigh
t(19
95)]
A.
McK
nigh
t,R
.A
.W
eiss
,C
.S
hotto
n,Y.
Take
uchi
,H
.H
oshi
no,
&P.
R.
Cla
pham
.C
hang
ein
trop
ism
upon
imm
une
esca
peby
hum
anim
mun
odefi
cien
cyvi
rus.J
Viro
l69:
3167
–317
0,19
95.
(Med
line:
9522
2771
).
[McL
ain
&D
imm
ock(
1994
)]L.
McL
ain
&N
.J.D
imm
ock.
Sin
gle-
and
mul
ti-hi
tkin
etic
sof
imm
unog
lobu
linG
neut
raliz
atio
nof
hum
anim
mun
odefi
cien
cyvi
rus
type
1by
mon
oclo
nala
ntib
odie
s.JG
en
Viro
l75:
1457
–146
0,19
94.
(Med
line:
9426
7431
).
[Met
las
(199
9a)]
R.M
etla
s,D
.Tra
jkov
ic,T
.Srd
ic,V
.Vel
jkov
ic,&
A.C
olom
-ba
tti.
Hum
anim
mun
odefi
cien
cyvi
rus
V3
pept
ide-
reac
tive
antib
odie
sar
epr
esen
tin
norm
alH
IV-n
egat
ive
sera
.A
IDS
Re
sH
um
Re
trov
iru
ses15:6
71–7
,19
99a.
(Med
line:
9926
0289
).
[Met
las
(199
9b)]
R.M
etla
s,D
.Tra
jkov
ic,T
.Srd
ic,V
.Vel
jkov
ic,&
A.C
olom
-ba
tti.
Ant
i-V3
and
anti-
IgG
antib
odie
sof
heal
thy
indi
vidu
als
shar
eco
m-
plem
enta
rity
stru
ctur
es.J
Acq
uir
Imm
un
eD
efic
Syn
dr21
:266
–70,
1999
b.(M
edlin
e:99
3550
57).
[Mha
shilk
ar(1
995)
]A
.M
.M
hash
ilkar
,J.
Bag
ley,
S.
Y.C
hen,
A.
M.
Szi
l-va
y,D
.G
.H
ella
nd,
&W
.A
.M
aras
co.
Inhi
bitio
nof
HIV
-1Ta
t-m
edia
ted
LTR
tran
sact
ivat
ion
and
HIV
-1in
fect
ion
byan
ti-Ta
tsi
ngle
chai
nin
trab
od-
ies.
EM
BO
J14
:154
2–15
51,
1995
.(M
edlin
e:95
2467
47)
Not
es:
Ant
i-Tat
intr
abod
ies
spec
ific
for
the
N-t
erm
inal
activ
atio
ndo
mai
nof
Tat,
bloc
kTa
t-m
edia
ted
tran
sact
ivat
ion
ofth
eH
IV-1
LTR
and
intr
acel
lula
rtr
affic
king
ofTa
tin
mam
mal
ian
cells
.Thu
ssi
ngle
chai
nin
trab
odie
sca
nef
fect
ivel
yta
rget
mol
ecul
esin
the
cyto
plas
man
dnu
clea
rco
mpa
rtm
ents
ofeu
kary
otic
cells
and
anti-
Tati
ntra
bodi
esm
aybe
usef
ulfo
rge
neth
erap
yof
HIV
-1in
fect
ion
and
AID
S.
[Mill
ar(1
998)
]A
.L.M
illar
,N.A
.Jac
kson
,H.D
alto
n,K
.R.J
enni
ngs,
M.L
evi,
B.W
ahre
n,&
N.J
.Dim
moc
k.R
apid
anal
ysis
ofep
itope
-par
atop
ein
tera
c-tio
nsbe
twee
nH
IV-1
and
a17
-am
ino-
acid
neut
raliz
ing
mic
roan
tibod
yby
elec
tros
pray
ioni
zatio
nm
ass
spec
trom
etry
.E
urJ
Bio
che
m258
:164
–9,1
998.
(Med
line:
9906
7031
).
[Mitc
hell
(199
8)]
W.
M.
Mitc
hell,
L.D
ing,
&J.
Gab
riel.
Inac
tivat
ion
ofa
com
mon
epito
pere
spon
sibl
efo
rth
ein
duct
ion
ofan
tibod
y-de
pend
ent
en-
hanc
emen
tofH
IV.A
IDS
12:1
47–5
6,19
98.
(Med
line:
9812
7881
).
[Mo
(199
7)]
H.
Mo,
L.S
tam
atat
os,
J.E
.Ip
,C
.F.
Bar
bas,
P.W
.H
.I.
Par
ren,
D.R
.Bur
ton,
J.P.
Moo
re,&
D.D
.Ho.
Hum
anim
mun
odefi
cien
cyvi
rus
type
1m
utan
tsth
ates
cape
neut
raliz
atio
nby
hum
anm
onoc
lona
lant
ibod
yIg
G1b
12.
JV
irol7
1:68
69–6
874,
1997
.(M
edlin
e:97
4047
00)N
otes
:AJR
CS
Fre
sist
ant
varia
ntw
asse
lect
edby
cultu
ring
inth
epr
esen
ceof
IgG
1b12
.The
resi
stan
tvi
rus
rem
aine
dse
nsiti
veto
2G12
and
2F5
and
toC
D4-
IgG
,enc
oura
ging
for
the
poss
ibili
tyof
com
bina
tion
ther
apy.
[Moj
a(2
000)
]P.
Moj
a,C
.T
ranc
hat,
I.T
chou
,B
.P
ozze
tto,
F.Lu
cht,
C.
Des
-gr
ange
s,&
C.G
enin
.Neu
tral
izat
ion
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
(HIV
-1)
med
iate
dby
paro
tidIg
Aof
HIV
-1-in
fect
edpa
tient
s[In
Pro
cess
Cita
tion]
.JIn
fect
Dis
181:
1607
–13,
2000
.(M
edlin
e:20
2837
27).
[Mom
any
(199
6)]
C.
Mom
any,
L.C
.K
ovar
i,A
.J.
Pro
ngay
,W
.K
elle
r,R
.K
.G
itti,
B.M
.Lee
,A.E
.Gor
bale
nya,
L.To
ng,J
.McC
lure
,L.S
.Ehr
lich,
M.F
.S
umm
ers,
C.C
arte
r,&
M.G
.Ros
sman
.C
ryst
alst
ruct
ure
ofdi
mer
icH
IV-1
caps
idpr
otei
n.N
atu
reS
tru
ctB
iol3:
763–
770,
1996
.(M
edlin
e:96
3787
87).
[Mon
dor
(199
8)]
I.M
ondo
r,S
.Ugo
lini,
&Q
.J.S
atte
ntau
.Hum
anim
mun
ode-
ficie
ncy
viru
sty
pe1
atta
chm
entt
oH
eLa
CD
4ce
llsis
CD
4in
depe
nden
tand
gp12
0de
pend
ent
and
requ
ires
cell
surf
ace
hepa
rans
.J
Viro
l72:
3623
–34,
1998
.(M
edlin
e:98
2167
21).
[Mon
tefio
ri&
Eva
ns(1
999)
]D
.Mon
tefio
ri&
T.E
vans
.Tow
ard
anH
IVTy
pe1
vacc
ine
that
gene
rate
spo
tent
broa
dly
cros
s-re
activ
ene
utra
lizin
gan
tibod
ies.
AID
SR
es
an
dH
um
an
Re
trov
iru
ses
15:6
89–9
8,19
99.(
Med
line:
9928
4356
).
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-28
DE
C20
00
[Mon
tefio
ri(1
993)
]D
.C
.M
onte
fiori,
B.
S.
Gra
ham
,J.
Zho
u,J.
Zho
u,R
.A
.B
ucco
,D
.H
.S
chw
artz
,L.
A.
Cav
acin
i,M
.R
.P
osne
r,&
the
NIH
-NIA
IDA
IDS
Vacc
ine
Clin
ical
Tria
lsN
etw
ork.
V3-
Spe
cific
Neu
tral
izin
gA
ntib
odie
sin
Ser
aF
rom
HIV
-1gp
160-
imm
uniz
edVo
lunt
eers
Blo
ckV
irus
Fus
ion
and
Act
Syn
ergi
stic
ally
with
Hum
anM
onoc
lona
lAnt
ibod
yto
the
Con
form
atio
n-de
pend
ent
CD
4B
indi
ngS
iteof
gp12
0.JC
linIn
vest
92:8
40–8
47,
1993
.(M
edlin
e:93
3528
32).
[Mon
tefio
ri(1
991)
]D
.C
.M
onte
fiori,
I.Y.
Zho
u,B
.B
arne
s,D
.La
ke,
E.
M.
Her
sh,Y
.Mas
uho,
&L.
B.L
efko
witz
Jr.
Hom
otyp
ican
tibod
yre
spon
ses
tofr
esh
clin
ical
isol
ates
ofhu
man
imm
unod
efici
ency
viru
s.V
irolo
gy
182:
635–
643,
1991
.(M
edlin
e:91
2207
13).
[Moo
re&
Trk
ola(
1997
)]J.
Moo
re&
A.T
rkol
a.H
IVty
pe1
core
cept
ors,
neu-
tral
izat
ion
sero
type
san
dva
ccin
ede
velo
pmen
t.A
IDS
Re
sH
um
Re
trov
iru
ses
13:7
33–7
36,1
997.
(Med
line:
9731
5042
).
[Moo
re(1
990)
]J.
P.M
oore
.S
impl
em
etho
dsfo
rm
onito
ring
HIV
-1an
dH
IV-
2gp
120
bind
ing
toso
lubl
eC
D4
byen
zym
e-lin
ked
imm
unos
orbe
ntas
say:
HIV
-2ha
sa
25-f
old
low
eraf
finity
and
HIV
-1fo
rso
lubl
eC
D4.A
IDS
NY
4:29
7,19
90.
(Med
line:
9027
4915
).
[Moo
re&
Bin
ley(
1998
)]J.
P.M
oore
&J.
Bin
ley.
HIV
Env
elop
e’s
lette
rsbo
xed
into
shap
e.Na
ture
393:
630–
631,
1998
.(M
edlin
e:98
3033
75)
Not
es:
Com
men
ton
Nat
ure
1998
Jun
18;3
93(6
686)
:648
-59
and
Nat
ure
1998
Jun
18;3
93(6
686)
:705
-11.
[Moo
re(1
994a
)]J.
P.M
oore
,Y.
Cao
,D
.D
.H
o,&
R.
A.
Kou
p.D
evel
op-
men
tof
the
anti-
gp12
0an
tibod
yre
spon
sedu
ring
sero
conv
ersi
onto
hum
anim
mun
odefi
cien
cyvi
rus
type
1.JV
irol6
8:51
42–5
155,
1994
a.(M
edlin
e:94
3091
81)N
otes
:Thr
eese
roco
nver
ting
indi
vidu
als
wer
est
udie
d.T
heea
rli-
estd
etec
tabl
ean
ti-gp
120
antib
odie
sw
ere
both
conf
orm
atio
nala
ndan
ti-V
3lo
op,a
ndco
uld
bede
tect
edon
lyaf
ter
the
peak
vire
mia
has
pass
ed.N
oun
i-fo
rmpa
ttern
ofau
tolo
gous
neut
raliz
ing
anti-
CD
4BS
oran
ti-V
3M
Abs
was
obse
rved
.
[Moo
re(1
995a
)]J.
P.M
oore
,Y.C
ao,L
.Qin
g,Q
.J.S
atte
ntau
,J.P
yati,
R.K
o-du
ri,J.
Rob
inso
n,C
.F.
Bar
bas
III,
D.
R.
Bur
ton,
&D
.D
.H
o.P
rimar
yis
olat
esof
hum
anim
mun
odefi
cien
cyvi
rus
type
Iar
ere
lativ
ely
resi
stan
tto
neut
raliz
atio
nby
mon
oclo
nala
ntib
odie
sto
gp12
0,an
dth
eirn
eutr
aliz
atio
nis
notp
redi
cted
byst
udie
sw
ithm
onom
eric
gp12
0.JV
irol6
9:10
1–10
9,19
95a.
(Med
line:
9507
4853
)N
otes
:A
pane
lof
anti-
gp12
0M
Abs
and
sera
from
HIV
-1in
fect
edin
divi
dual
sw
aste
sted
for
itsab
ility
tone
utra
lize
prim
ary
isol
ates
.Mos
tMA
bsbo
und
with
high
affin
ityto
gp12
0m
onom
ers
from
the
vario
usis
olat
es,b
utw
ere
note
ffect
ive
atne
utra
lizin
g.T
heM
Ab
IgG
1b12
,w
hich
bind
sto
adi
scon
tinuo
usan
ti-C
D4
bind
ing
site
epito
pe,
was
able
tone
utra
lize
mos
toft
hepr
imar
yis
olat
es.
[Moo
re&
Ho(
1993
)]J.
P.M
oore
&D
.D.H
o.A
ntib
odie
sto
disc
ontin
uous
orco
nfor
mat
iona
llyse
nsiti
veep
itope
son
the
gp12
0gl
ycop
rote
inof
hum
anim
-m
unod
efici
ency
viru
sty
pe1
are
high
lypr
eval
enti
nse
raof
infe
cted
hum
ans.
JV
irol6
7:86
3–87
5,19
93.
(Med
line:
9312
4581
)N
otes
:CD
4BS
antib
odie
sar
epr
eval
ent
inH
IV-1
-pos
itive
sera
,w
hile
neut
raliz
ing
MA
bsto
C4,
V2,
and
V3
and
MA
bsto
linea
rep
itope
sar
ele
ssco
mm
on.M
ostl
inea
rep
itope
MA
bsin
hum
anse
raar
edi
rect
edag
ains
tthe
V3
regi
on,a
ndcr
oss-
reac
tive
MA
bste
ndto
bedi
rect
edag
ains
tdis
cont
inuo
usep
itope
s.
[Moo
re&
Ho(
1995
)]J.
P.M
oore
&D
.D.H
o.H
IV-1
neut
raliz
atio
n:th
eco
n-se
quen
ces
ofad
apta
tion
togr
owth
ontr
ansf
orm
edT-
cells
.A
IDS
9su
ppl
A:S
117–
S13
6,19
95.(
Med
line:
9641
6784
)Not
es:T
his
revi
ewco
nsid
ers
the
rela
tive
impo
rtan
ceof
ane
utra
lizin
gan
tibod
yre
spon
sefo
rthe
deve
lopm
ent
ofa
vacc
ine,
and
for
dise
ase
prog
ress
ion
durin
gth
ech
roni
cph
ase
ofH
IV-1
infe
ctio
n.It
sugg
ests
that
T-ce
llim
mun
itym
aybe
mor
eim
port
ant.
The
dis-
tinct
ion
betw
een
MA
bsth
atca
nne
utra
lize
prim
ary
isol
ates
,an
dth
ose
that
are
effe
ctiv
eat
neut
raliz
ing
only
labo
rato
ryad
apte
dst
rain
sis
disc
usse
din
deta
il.A
ltern
ativ
eco
nfor
mat
ions
ofen
velo
pean
dno
n-co
ntig
uous
inte
ract
-in
gdo
mai
nsin
gp12
0ar
edi
scus
sed.
The
sugg
estio
nth
atso
lubl
em
onom
eric
gp12
0m
ayse
rve
asa
vira
ldec
oyth
atdi
vert
sth
ehu
mor
alim
mun
ere
spon
seit
invi
vois
putf
orth
.
[Moo
re(1
994b
)]J.
P.M
oore
,F.E
.McC
utch
an,S
.-W
.Poo
n,J.
Mas
cola
,J.L
iu,
Y.C
ao,&
D.D
.Ho.
Exp
lora
tion
ofan
tigen
icva
riatio
nin
gp12
0fr
omcl
ades
Ath
roug
hF
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
byus
ing
mon
oclo
nal
antib
odie
s.J
Viro
l68:
8350
–836
4,19
94b.
(Med
line:
9505
6067
)Not
es:F
our
offiv
ean
ti-V
3M
Abs
wer
esl
ight
lycr
oss-
reac
tive
with
incl
ade
B,
but
not
very
reac
tive
outs
ide
clad
eB
.Tw
odi
scon
tinuo
usC
D4
bind
ing
site
Mab
sap
pear
tobe
pan-
reac
tive.
Ant
i-V2
MA
bsw
ere
only
spor
adic
ally
reac
tive
insi
dean
dou
tsid
eof
clad
eB
.
[Moo
re(1
990)
]J.
P.M
oore
,J.A
.McK
eatin
g,R
.A.W
eiss
,&Q
.J.S
atte
ntau
.D
isso
ciat
ion
ofgp
120
from
HIV
-1vi
rions
indu
ced
byso
lubl
eC
D4.Sci
en
ce25
0:11
39–1
142,
1990
.(M
edlin
e:91
0680
08).
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-29
DE
C20
00
[Moo
re(1
994c
)]J.
P.M
oore
,Q.J
.Sat
tent
au,R
.Wya
tt,&
J.S
odro
ski.
Pro
bing
the
Str
uctu
reof
the
Hum
anIm
mun
odefi
cien
cyV
irus
Sur
face
Gly
copr
otei
ngp
120
with
aP
anel
ofm
onoc
lona
lant
ibod
ies.JV
irol6
8:46
9–48
4,19
94c.
(Med
line:
9407
6440
)Not
es:.
Thi
sst
udy
com
pare
da
larg
enu
mbe
rofM
Abs
that
bind
tolin
ear
epito
pes
ofgp
120,
and
com
pare
dbi
ndin
gaf
finiti
esfo
r:i)
nativ
ean
dS
DS
-DD
Tde
natu
red
gp12
0,(c
lone
BH
10of
the
LAI
isol
ate
expr
esse
din
CH
Oce
lls);
ii)re
com
bina
ntgp
120
lack
ing
the
V1,
V2,
V3
loop
s;iii
)a
pane
lof
20m
erpe
ptid
es;
iv)
apa
nel
ofgp
120
mut
ants
;an
dv)
olig
omer
icve
rsus
mon
omer
icgp
120.
The
bind
ing
ratio
ofna
tive
vers
usde
natu
red
mon
omer
icgp
120
isin
clud
edin
the
tabl
ein
this
data
base
.The
senu
mbe
rssh
ould
beco
nsid
ered
with
the
follo
win
gpo
ints
inm
ind:
aco
n-tin
uous
epito
pem
aybe
part
ially
expo
sed
onth
esu
rfac
e;an
da
prep
arat
ion
ofrg
p120
isno
tho
mog
eneo
usan
dco
ntai
nsfu
llyfo
lded
,pa
rtly
dena
ture
d,an
dso
me
com
plet
ely
unfo
lded
spec
ies,
soth
eco
nfor
mat
ion
ofw
hati
sco
n-si
dere
dto
bea
nativ
epr
otei
nw
illno
ton
lyre
flect
fully
fold
edgp
120.
The
auth
ors
sugg
estt
hata
fivef
old
incr
ease
inth
eaf
finity
for
aM
Ab
bind
ing
tode
natu
red
vers
usna
tive
gp12
0in
dica
tes
that
the
epito
peis
inac
cess
ible
inth
ena
tive
form
.We
also
have
incl
uded
here
info
rmat
ion
extr
acte
dfr
omM
oore
et
al‘s
list
ofth
egp
120
mut
atio
nsth
atre
duce
dth
ebi
ndin
gof
apa
rtic
ular
MA
b.In
map
ping
ofex
pose
dre
gion
sof
gp12
0,C
2,C
3,an
dC
5do
mai
nep
itope
sw
ere
foun
dto
bind
pref
eren
tially
tode
natu
red
gp12
0.V
1,V
2an
dV
3,pa
rtof
C4,
and
the
extr
eme
carb
oxy
term
inus
ofC
5w
ere
expo
sed
onth
ena
tive
mon
omer
.In
the
olig
omer
icfo
rmof
the
mol
ecul
e,on
lyV
2,V
3an
dpa
rtof
C4
are
wel
lexp
osed
asco
ntin
uous
epito
pes.
[Moo
re(1
993a
)]J.
P.M
oore
,Q
.J.
Sat
tent
au,
H.
Yosh
iyam
a,M
.T
hali,
M.C
harle
s,N
.Sul
livan
,S.-
W.P
oon,
M.S
.Fun
g,F.
Tra
inca
rd,M
.Pin
kus,
G.
Rob
ey,
J.E
.R
obin
son,
D.
D.
Ho,
&J.
Sod
rosk
i.P
robi
ngth
est
ruct
ure
ofth
eV
2do
mai
nof
hum
anim
mun
odefi
cien
cyvi
rus
type
1su
rfac
egl
yco-
prot
ein
gp12
0w
itha
pane
lofe
ight
mon
oclo
nala
ntib
odie
s:hu
man
imm
une
resp
onse
toth
eV
1an
dV
2do
mai
ns.
JV
irol6
7:61
36–6
151,
1993
a.(M
edlin
e:93
3818
17).
[Moo
re&
Sod
rosk
i(199
6)]
J.P.
Moo
re&
J.S
odro
ski.
Ant
ibod
ycr
oss-
com
petit
ion
anal
ysis
ofth
ehu
man
imm
unod
efici
ency
viru
sty
pe1
gp12
0ex
terio
ren
velo
pegl
ycop
rote
in.J
Viro
l70
:186
3–18
72,
1996
.(M
edlin
e:96
1905
89)
Not
es:
46an
ti-gp
120
mon
omer
MA
bsw
ere
used
tocr
eate
aco
mpe
titio
nm
atrix
,an
dM
Ab
com
petit
ion
grou
psw
ere
defin
ed.
The
data
sugg
ests
that
ther
ear
etw
ofa
ces
ofth
egp
120
glyc
opro
tein
:afa
ceoc
cupi
edby
the
CD
4BS
,whi
chis
pres
umab
lyal
soex
pose
don
the
olig
omer
icen
velo
pe
glyc
opro
tein
com
plex
,and
ase
cond
face
whi
chis
pres
umab
lyin
acce
ssib
leon
the
olig
omer
and
inte
ract
sw
itha
num
ber
ofno
nneu
tral
izin
gan
tibod
ies.
[Moo
re(1
993b
)]J.
P.M
oore
,M
.T
hali,
B.
A.
Jam
eson
,F.
Vig
naux
,G
.K
.Le
wis
,S.-
W.P
oon,
M.S
.Fun
g,P.
J.D
urda
,L.A
kerb
lom
,B.W
ahre
n,D
.D.
Ho,
Q.J
.Sat
tent
au,&
J.S
odro
ski.
Imm
unoc
hem
ical
anal
ysis
ofth
egp
120
surf
ace
glyc
opro
tein
ofhu
man
imm
unod
efici
ency
viru
sty
pe1:
Pro
bing
the
stru
ctur
eof
the
C4
and
V4
dom
ains
and
the
inte
ract
ion
ofth
eC
4do
mai
nw
ithth
eV
3lo
op.
JV
irol
73:4
785–
4796
,19
93b.
(Med
line:
9332
3221
)N
otes
:Gen
eral
obse
rvat
ions
:C4
and
V3
MA
bsar
ese
nsiti
veto
the
way
the
epito
pes
are
pres
ente
d,an
dth
isse
nsiti
vity
cann
otbe
corr
elat
edto
pept
ide
bind
ing.
Som
eV
3-C
4do
mai
nin
tera
ctio
nw
asin
dica
ted
base
don
mut
atio
nan
din
terf
eren
cest
udie
s.
[Moo
re(1
995b
)]J.
P.M
oore
,A.T
rkol
a,B
.Kor
ber,
L.J.
Boo
ts,J
.A.K
essl
erII,
F.E
.McC
utch
an,J
.Mas
cola
,D.D
.Ho,
J.R
obin
son,
&A
.J.C
onle
y.A
hum
anm
onoc
lona
lant
ibod
yto
aco
mpl
exep
itope
inth
eV
3re
gion
ofgp
120
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
has
broa
dre
activ
ityw
ithin
and
outs
ide
clad
eB
.JV
irol6
9:12
2–13
0,19
95b.
(Med
line:
9507
4855
)N
otes
:T
heep
itope
was
defin
edas
incl
udin
gam
ino
acid
son
both
side
sof
the
loop
ofth
eV
3lo
op:
-I—
-G–F
Y-T,
whe
reth
eG
isth
ese
cond
Gof
the
GP
GR
tipof
the
loop
.T
his
antib
ody
boun
dw
ellt
ogp
120
mol
ecul
esfr
omcl
ades
A,B
,C,E
,and
F,w
hen
the
criti
cala
min
oac
ids
wer
epr
esen
t.B
indi
ngdi
dno
tpa
ralle
lneu
tral
izat
ion
how
ever
;19
bco
uld
prod
uce
a50
-fol
dre
duct
ion
ofin
fect
ivity
inso
me
prim
ary
Bis
olat
es,
and
inC
clad
eis
olat
esat
low
viru
sin
putc
once
ntra
tions
,but
noti
nis
olat
esfr
omal
lcla
des
whe
rebi
ndin
gco
uld
occu
r(A
,E,a
ndF
).
[Moo
re(1
994d
)]J.
P.M
oore
,R.L
.Will
ey,G
.K.L
ewis
,J.R
obin
son,
&J.
So-
dros
ki.
Imm
unol
ogic
alev
iden
cefo
rin
tera
ctio
nsbe
twee
nth
efir
st,
seco
ndan
dfif
thco
nser
ved
dom
ains
ofth
egp
120
surf
ace
glyc
opro
tein
ofhu
man
imm
unod
efici
ency
viru
sty
pe1.J
Viro
l68:
6836
–684
7,19
94d.
(Med
line:
9501
8590
)N
otes
:M
utat
ion
267N
/Qin
C2
regi
onre
sults
inex
posi
ngth
eca
rbox
y-te
rmin
alen
dgp
120.
[Moo
re(1
993c
)]J.
P.M
oore
,H.Y
oshi
yam
a,D
.D.H
o,J.
E.R
obin
son,
&J.
So-
dros
ki.
Ant
igen
icva
riatio
nin
gp12
0sfr
omm
olec
ular
clon
esof
HIV
-1LA
I.A
IDS
Re
sH
um
Re
trov
iru
ses9:11
85–1
193,
1993
c.(M
edlin
e:94
1906
23)
Not
es:T
hebi
ndin
gof
MA
bsto
four
mol
ecul
arcl
ones
ofH
IV-1
LAI:
HxB
2,H
xB3,
Hx1
0,an
dN
L4-3
,was
mea
sure
d.D
espi
teth
ecl
ose
rela
tions
hip
be-
twee
nth
ese
clon
es,t
here
isco
nsid
erab
leva
riatio
nin
thei
rant
igen
icst
ruct
ure,
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-30
DE
C20
00
judg
edby
MA
bre
activ
ities
toth
eV
2,V
3,an
dC
4do
mai
nsan
dto
disc
ontin
u-ou
sep
itope
s.S
mal
lvar
iatio
nsin
sequ
ence
can
prof
ound
lyaf
fect
reco
gniti
onof
gp12
0by
allfi
vegr
oups
ofde
fined
anti-
gp12
0ne
utra
lizin
gan
tibod
ies.
[Mor
an(1
993)
]M
.J.
Mor
an,
J.S
.A
ndris
,Y.
-I.
Mat
sum
ato,
J.D
.C
apra
,&
E.
M.
Her
sh.
Varia
ble
regi
onge
nes
ofan
ti-H
IVhu
man
mon
oclo
nala
nti-
bodi
es:
Non
-res
tric
ted
use
ofth
eV
gene
repe
rtoi
rean
dex
tens
ive
som
atic
mut
atio
n.M
olI
mm
un
ol3
0:15
43–1
551,
1993
.(M
edlin
e:94
0498
45)
Not
es:
Seq
uenc
edva
riabl
ere
gion
sfr
omfo
urhu
man
anti-
HIV
-1M
Abs
:ant
i-gp1
2013
,S1-
1an
dH
BW
4;an
dan
ti-gp
41N
o.86
.Ext
ensi
veso
mat
icm
utat
ion
was
obse
rved
and
unde
r-re
pres
enta
tion
ofV
HIII
usag
e.
[Mor
ner
(199
9)]
A.M
orne
r,A
.Ach
our,
M.N
orin
,R.T
hors
tens
son,
&E
.Bjo
r-lin
g.F
ine
char
acte
rizat
ion
ofa
V3-
regi
onne
utra
lizin
gep
itope
inhu
man
imm
unod
efici
ency
viru
sty
pe2
[InP
roce
ssC
itatio
n].
Viru
sR
es5
9:49
–60,
1999
.(M
edlin
e:20
3112
26).
[Muh
lbac
her
(199
9)]
M.
Muh
lbac
her,
M.
Spr
uth,
F.S
iege
l,R
.Z
ange
rle,
&M
.P.D
ieric
h.Lo
ngitu
dina
lstu
dyof
antib
ody
reac
tivity
agai
nstH
IV-1
enve
-lo
pean
da
pept
ide
repr
esen
ting
aco
nser
ved
site
onG
p41
inH
IV-1
-infe
cted
patie
nts.
Imm
un
ob
iolo
gy2
00:2
95–3
05,1
999.
(Med
line:
9934
4625
).
[Mul
ler
(199
1)]
S.
Mul
ler,
H.-
T.W
ang,
S.-
V.K
aver
i,S
.C
hatto
padh
yay,
&H
.Koh
ler.
Gen
erat
ion
and
Spe
cific
ityof
Mon
oclo
nalA
nti-I
diot
ypic
Ant
i-bo
dies
Aga
inst
Hum
anH
IV-S
peci
ficA
ntib
odie
s.JIm
mu
no
l147
:933
–941
,19
91.
(Med
line:
9131
8181
).
[Mus
ter
(199
5)]
T.M
uste
r,B
.F
erko
,A
.K
lima,
M.
Pur
tsch
er,
A.
Trk
ola,
P.S
chul
z,A
.G
rass
auer
,O
.G
.E
ngle
hard
,A
.G
arci
a-S
astr
e,P.
Pal
ese,
&H
.Kat
inge
r.M
ucos
alM
odel
ofIm
mun
izat
ion
agai
nsth
uman
imm
unod
efi-
cien
cyvi
rus
type
1w
itha
chim
eric
influ
enza
viru
s.JV
irol6
9:66
78–6
686,
1995
.(M
edlin
e:96
0137
60).
[Mus
ter
(199
4)]
T.M
uste
r,R
.G
uine
a,A
.T
rkol
a,M
.P
urts
cher
,A
.K
lima,
F.S
tein
dl,
P.P
ales
e,&
H.
Kat
inge
r.C
ross
-Neu
tral
izat
ion
activ
ityag
ains
tdi
verg
enth
uman
imm
unod
efici
ency
viru
sty
pe1
isol
ates
indu
ced
byth
egp
41se
quen
ceE
LDK
WA
S.J
Viro
l68:
4031
–403
4,19
94.
(Med
line:
9424
6751
).
[Mus
ter
(199
3)]
T.M
uste
r,F.
Ste
indl
,M
.P
urts
cher
,A
.T
rkol
a,A
.K
lima,
G.
Him
mle
r,F.
Ruk
er,
&H
.K
atin
ger.
Aco
nser
ved
neut
raliz
ing
epito
peon
gp41
ofhu
man
imm
unod
efici
ency
viru
sty
pe1.JV
irol6
7:66
42–6
647,
1993
.(M
edlin
e:94
0168
48)
Not
es:
Pep
tides
cont
aini
ngth
eam
ino
acid
se-
quen
ceLD
KW
AS
orD
KW
AS
Lsh
owed
redu
ced
reac
tivity
.T
hepe
ptid
es
LELD
KW
and
KW
AS
LWsh
owed
nosi
gnifi
cant
reac
tion.
The
seda
tasu
g-ge
stth
atth
eep
itope
ofth
eM
Ab
2F5
com
pris
esth
eam
ino
acid
sequ
ence
ELD
KW
A,w
ithD
KW
Abe
ing
the
core
sequ
ence
.
[Mye
rs(1
993)
]R
.M
yers
,T.
Mei
ller,
W.
Fal
kler
,J.
Pat
el,
&J.
Jose
ph.
Ahu
man
mon
oclo
nal
antib
ody
toa
cryp
ticgp
41ep
itope
onH
IV-1
infe
cted
cells
.A
bst
rG
en
Me
et
Am
So
cM
icro
bio
l93:4
44,
1993
.N
otes
:A
idsl
ine:
9329
1838
Abs
trac
tT70
.
[Nak
amur
a(1
992)
]G
.R.N
akam
ura,
R.B
yrn,
K.R
osen
thal
,J.P
.Por
ter,
M.R
.H
obbs
,L.R
iddl
e,D
.J.E
astm
an,D
.Dow
benk
o,T.
Gre
gory
,B.M
.Fen
dly,
&P.
W.B
erm
an.
Mon
oclo
nala
ntib
odie
sto
the
extr
acel
lula
rdo
mai
nof
HIV
-1III
Bgp
160
that
neut
raliz
ein
fect
ivity
,blo
ckbi
ndin
gto
CD
4,an
dre
actw
ithdi
vers
eis
olat
es.AID
SR
es
Hu
mR
etr
oviru
ses8:18
75–1
885,
1992
.(M
edlin
e:93
1439
97).
[Nak
amur
a(1
993)
]G
.R.N
akam
ura,
R.B
yrn,
D.M
.Wilk
es,J
.A.F
ox,M
.R.
Hob
bs,R
.Has
tings
,H.C
.Wes
slin
g,M
.A.N
orcr
oss,
B.M
.Fen
dly,
&P.
W.
Ber
man
.S
trai
nsp
ecifi
city
and
bind
ing
affin
ityre
quire
men
tsof
neut
raliz
ing
mon
oclo
nala
ntib
odie
sto
the
C4
dom
ain
ofgp
120
from
hum
anim
mun
od-
efici
ency
viru
sty
pe1.
JV
irol6
7:61
79–6
191,
1993
.(M
edlin
e:93
3818
21)
Not
es:
Mul
tiple
CD
4bi
ndin
gdo
mai
nan
tibod
ies
are
desc
ribed
;on
lyon
eha
sa
linea
rpe
ptid
ere
activ
ity(1
3H8)
.A
V3
loop
bind
ing
antib
ody
isal
sode
scrib
ed(1
026)
.
[Nar
a(1
990)
]P.
L.N
ara,
L.S
mit,
N.D
unlo
p,W
.Hat
ch,M
.Mer
ges,
D.W
ater
s,J.
Kel
liher
,R
.C
.G
allo
,P.
J.F
isch
inge
r,&
J.G
ouds
mit.
Em
erge
nce
ofvi
ruse
sre
sist
antt
one
utra
lizat
ion
byV
3-sp
ecifi
can
tibod
ies
inex
perim
enta
lhu
man
imm
unod
efici
ency
viru
sty
pe1
IIIB
infe
ctio
nof
chim
panz
ees.
JV
irol
64:3
779–
3791
,199
0.(M
edlin
e:90
3178
76).
[Nes
hat(
2000
)]M
.N
.N
esha
t,L.
Goo
dglic
k,K
.Li
m,
&J.
Bra
un.
Map
ping
the
Bce
llsu
pera
ntig
enbi
ndin
gsi
tefo
rH
IV-1
gp12
0on
aV
(H)3
Ig.
Int
Imm
un
ol1
2:30
5–12
,200
0.(M
edlin
e:20
1669
82).
[Neu
rath
(199
5)]
A.
R.
Neu
rath
,N
.S
tric
k,K
.Li
n,&
S.
Jian
g.M
ultif
acet
edco
nseq
uenc
esof
anti-
gp41
mon
oclo
nala
ntib
ody
2F5
bind
ing
toH
IVty
pe1
virio
ns.
AID
SR
es
Hu
mR
etr
oviru
ses11
:687
–96,
1995
.(M
edlin
e:96
0782
29).
[Nie
drig
(199
2a)]
M.N
iedr
ig,M
.Bro
ker,
G.W
alte
r,W
.Stu
ber,
H.-
P.H
arth
us,
S.
Meh
di,
H.
R.
Gel
derb
lom
,&
G.
Pau
li.M
urin
em
onoc
lona
lan
tibod
ies
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-31
DE
C20
00
dire
cted
agai
nst
the
tran
smem
bran
epr
otei
ngp
41of
hum
anim
mun
odefi
-ci
ency
viru
sty
pe1
enha
nce
itsin
fect
ivity
.JG
en
Viro
l73:
951–
954,
1992
a.(M
edlin
e:92
3410
76).
[Nie
drig
(199
2b)]
M.N
iedr
ig,H
.-P.
Har
thus
,M.B
roke
r,H
.Bic
khar
d,G
.Pau
li,H
.R
.G
elde
rblo
m,
&B
.W
ahre
n.In
hibi
tion
ofvi
ralr
eplic
atio
nby
mon
o-cl
onal
antib
odie
sdi
rect
edag
ains
thum
anim
mun
odefi
cien
cyvi
rus
gp12
0.J
Ge
nV
irol7
3:24
51–2
455,
1992
b.(M
edlin
e:93
0190
73).
[Nie
drig
(199
1)]
M.
Nie
drig
,J.
Hin
kula
,H
.-P.
Har
thus
,M
.B
roke
r,L.
Hop
p,G
.Pau
li,&
B.W
ahre
n.C
hara
cter
izat
ion
ofm
urin
em
onoc
lona
lant
ibod
ies
dire
cted
agai
nstt
heco
repr
otei
nsof
hum
anim
mun
odefi
cien
cyvi
rus
type
s1
and
2.J
Viro
l65:
4529
–453
3,19
91.
(Med
line:
9130
3716
)N
otes
:Mul
tiple
anti-
HIV
p24
MA
bsw
ere
gene
rate
dus
ing
HIV
-1III
Bp2
4or
HIV
-2R
OD
p26
asim
mun
ogen
s.T
heep
itope
sfo
rth
ese
MA
bsw
ere
map
ped,
and
the
cros
s-re
activ
itybe
twee
nH
IV-1
IIIB
,H
IV-2
RO
Dan
dS
IVM
AC
antig
ens
wer
eco
mpa
red
usin
gm
ultip
lean
tibod
ybi
ndin
gas
says
.Whi
leso
me
ofth
ean
tibod
ies
rais
edw
ere
cros
s-re
activ
eby
som
eor
allo
fthe
assa
ys,(
ELI
SA
,W
B,
imm
unofl
uore
scen
ce,
imm
unop
reci
pita
tion
and
alka
line
phos
phat
ase
anti-
alka
line
phos
phat
ase
assa
y),
the
diffe
rent
assa
ysof
ten
gave
diffe
rent
resu
lts.
Onl
yth
ean
tibod
ies
rais
edto
HIV
-1III
Bp2
4ar
ein
clud
edin
this
data
base
.
[Nie
drig
(198
9)]
M.N
iedr
ig,J
.Hin
kula
,W.W
eige
lt,J.
L’A
ge-S
tehr
,G.P
auli,
J.R
osen
,&B
.Wah
ren.
Epi
tope
map
ping
ofm
onoc
lona
lant
ibod
ies
agai
nst
hum
anim
mun
odefi
cien
cyvi
rus
type
1st
ruct
ural
prot
eins
byus
ing
pept
ides
.J
Viro
l63:
3525
–352
8,19
89.
(Med
line:
8931
1648
)N
otes
:M
ultip
lelin
ear
MA
bep
itope
sw
ere
desc
ribed
inp2
4an
dp1
7.S
ever
alM
Abs
wer
eab
leto
reac
tw
ithH
IV-2
RO
Dan
dS
IVM
AC
inan
imm
unob
lot
assa
y,as
wel
las
with
HIV
-1.
[Nie
drig
(198
8)]
M.N
iedr
ig,J
.-P.
Rab
anus
,J.L
.Ste
hr,H
.R.G
elde
rblo
m,&
G.P
auli.
Mon
oclo
nala
ntib
odie
sdi
rect
edag
ains
thum
anim
mun
odefi
cien
cyvi
rus
gag
prot
eins
with
spec
ifici
tyfo
rco
nser
ved
epito
pes
inH
IV-1
,H
IV-
2an
dsi
mia
nim
mun
odefi
cien
cyvi
rus.J
Ge
nV
irol6
9:21
09–2
114,
1988
.(M
edlin
e:88
2999
73).
[Nils
en(1
996)
]B
.M.N
ilsen
,I.R
.Hau
gan,
K.B
erg,
L.O
lsen
,P.O
.Bro
wn,
&D
.E
.H
ella
nd.
Mon
oclo
nalA
ntib
odie
sag
ains
tH
uman
Imm
unod
efici
ency
viru
sty
pe1
inte
gras
e:ep
itope
map
ping
and
diffe
rent
iale
ffect
sof
inte
gras
eac
tiviti
esin
vitr
o.J
Viro
l70:
1580
–158
7,19
96.
(Med
line:
9619
0555
)Not
es:
Inth
isst
udy,
17an
ti-in
tegr
ase
mur
ine
Mab
sw
ere
gene
rate
dan
dep
itope
s
wer
em
appe
dby
dele
tion
mut
atio
nsan
dpe
ptid
esc
anni
ng.
The
abili
tyof
MA
bbi
ndin
gto
inhi
bit(
orst
imul
ate)
end-
proc
essi
ng,D
NA
join
ing,
rein
te-
grat
ion,
and
disi
nteg
ratio
nen
zym
efu
nctio
nsit
invi
tro
was
dete
rmin
ed.
[Nya
mbi
(199
8)]
P.N
.Nya
mbi
,M.K
.Gor
ny,L
.Bas
tiani
,G.v
ande
rG
roen
,C
.W
illia
ms,
&S
.Z
olla
-Paz
ner.
Map
ping
ofep
itope
sex
pose
don
inta
cthu
man
imm
unod
efici
ency
viru
sty
pe1
(HIV
-1)
virio
ns:
ane
wst
rate
gyfo
rst
udyi
ngth
eim
mun
olog
icre
late
dnes
sof
HIV
-1.
JV
irol7
2:93
84–9
1,19
98.
(Med
line:
9844
0613
)N
otes
:18
hum
anM
Abs
bind
ing
togp
120
and
gp41
wer
ete
sted
usin
ga
nove
lass
ayto
test
bind
ing
toin
tact
HIV
-1vi
rions
.The
new
met
hod
invo
lves
usin
gM
Abs
toth
eho
stpr
otei
nsin
corp
orat
edin
tovi
rions
tobi
ndth
emto
ELI
ZA
plat
es.
Ant
igen
icco
nser
vatio
nin
epito
pes
ofH
IV-1
incl
ades
A,
B,
D,
F,G
,an
dH
was
stud
ied.
MA
bsw
ere
sele
cted
that
wer
edi
rect
edag
ains
tV2,
V3,
CD
4bd,
C5
orgp
41re
gion
s.A
ntib
odie
sag
ains
tV
2,th
eC
D4B
S,
and
sp41
show
edw
eak
and
spor
adic
reac
tiviti
es,
whi
lebi
ndin
gst
rong
lyto
gp12
0,su
gges
ting
thes
eep
itope
sar
ehi
dden
whe
ngp
120
isin
itsna
tive,
quat
erna
ryst
ruct
ure.
[Nya
mbi
(200
0)]
P.N
.N
yam
bi,
H.
A.
Mba
h,S
.B
urda
,C
.W
illia
ms,
M.
K.
Gor
ny,
A.
Nad
as,
&S
.Z
olla
-Paz
ner.
Con
serv
edan
dex
pose
dep
itope
son
inta
ct,n
ativ
e,pr
imar
yhu
man
imm
unod
efici
ency
viru
sty
pe1
virio
nsof
grou
pM
.J
Viro
l74:
7096
–107
,200
0.(M
edlin
e:20
3473
73).
[Ogg
ioni
(199
9)]
M.
R.
Ogg
ioni
,D
.M
edag
lini,
L.R
oman
o,F.
Per
uzzi
,T.
Mag
gi,L
.Loz
zi,L
.Bra
cci,
M.Z
azzi
,F.M
anca
,P.E
.Val
ensi
n,&
G.P
ozzi
.A
ntig
enic
ityan
dim
mun
ogen
icity
ofth
eV
3do
mai
nof
HIV
type
1gl
yco-
prot
ein
120
expr
esse
don
the
surf
ace
ofS
trep
toco
ccus
gord
onii.
AID
SR
es
Hu
mR
etr
oviru
ses1
5:45
1–9,
1999
.(M
edlin
e:99
2101
30).
[O’H
agan
(200
0)]
D.
T.O
’Hag
an,
M.
Ugo
zzol
i,J.
Bar
ackm
an,
M.
Sin
gh,
J.K
azza
z,K
.H
iggi
ns,
T.C
.Va
ncot
t,&
G.
Ott.
Mic
ropa
rtic
les
inM
F59
,a
pote
ntad
juva
ntco
mbi
natio
nfo
ra
reco
mbi
nant
prot
ein
vacc
ine
agai
nst
HIV
-1.
Va
ccin
e18:
1793
–801
,200
0.(M
edlin
e:20
1651
32).
[Ohl
in(1
989)
]M
.Ohl
in,P
.-A
.Bro
liden
,L.D
anie
lsso
n,B
.Wah
ren,
J.R
osen
,M
.Jon
dal,
&C
.A.K
.Bor
reba
eck.
Hum
anm
onoc
lona
lant
ibod
ies
agai
nst
are
com
bina
ntH
IVen
velo
pean
tigen
prod
uced
bypr
imar
yin
vitr
oim
mu-
niza
tion.
Cha
ract
eriz
atio
nan
dep
itope
map
ping
.Im
mu
no
log
y68:
325–
331,
1989
.(M
edlin
e:90
0775
07).
[Ohl
in(1
992)
]M
.O
hlin
,J.
Hin
kula
,P.
-A.
Bro
liden
,R
.G
runo
w,
C.
A.
K.
Bor
reba
eck,
&B
.Wah
ren.
Hum
anM
oAbs
prod
uced
from
norm
al,H
IV-1
-
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-32
DE
C20
00
nega
tive
dono
rsan
dsp
ecifi
cfo
rgl
ycop
rote
ingp
120
ofth
eH
IV-1
enve
lope
.C
linE
xpIm
mu
no
l89:
290–
295,
1992
.(M
edlin
e:92
3469
04).
[Ohn
o(1
991)
]T.
Ohn
o,M
.Te
rada
,Y.
Yone
da,
K.
W.
She
a,R
.F.
Cha
mbe
rs,
D.M
.Str
oka,
M.N
akam
ura,
&D
.W.K
ufe.
Abr
oadl
yne
utra
lizin
gm
ono-
clon
alan
tibod
yth
atre
cogn
izes
the
V3
regi
onof
hum
anim
mun
odefi
cien
cyvi
rus
type
1gl
ycop
rote
ingp
120.P
roc
Na
tlA
cad
Sci
US
A88:
1072
6–10
729,
1991
.(M
edlin
e:92
0733
60).
[Oka
da(1
994)
]T.
Oka
da,B
.K.P
atte
rson
,P.
A.O
tto,&
M.E
.Gur
ney.
HIV
Type
1In
fect
ion
ofC
D4+
T-ce
llsD
epen
dsC
ritic
ally
onB
asic
Am
ino
Aci
dR
esid
ues
inth
eV
3D
omai
nof
Env
elop
eG
lyco
prot
ein
120.
AID
SR
es
Hu
mR
etr
oviru
ses1
0:80
3–81
1,19
94.
(Med
line:
9507
7999
).
[Oka
mot
o(1
998)
]Y.
Oka
mot
o,Y.
Eda
,A
.O
gura
,S
.S
hiba
ta,
T.A
mag
ai,
Y.K
atsu
ra,
T.A
sano
,K
.K
imac
hi,
K.
Mak
izum
i,&
M.
Hon
da.
InS
CID
-hu
mic
e,pa
ssiv
etr
ansf
erof
ahu
man
ized
antib
ody
prev
ents
infe
ctio
nan
dat
roph
icch
ange
ofm
edul
lain
hum
anth
ymic
impl
antd
ueto
intr
aven
ous
in-
ocul
atio
nof
prim
ary
HIV
-1is
olat
e.JIm
mu
no
l160
:69–
76,1
998.
(Med
line:
9821
1683
).
[Old
ston
e(1
991)
]M
.B.A
.Old
ston
e,A
.Tis
hon,
H.L
ewic
ki,H
.J.D
yson
,V.A
.F
eher
,N.A
ssa-
Mun
t,&
P.E
.Wrig
ht.
Map
ping
the
anat
omy
ofth
eim
mun
-od
omin
ant
dom
ain
ofth
ehu
man
imm
unod
efici
ency
viru
sgp
41tr
ansm
em-
bran
epr
otei
n:pe
ptid
eco
nfor
mat
ion
anal
ysis
usin
gm
onoc
lona
lant
ibod
ies
and
prot
onnu
clea
rmag
netic
reso
nanc
esp
ectr
osco
py.
JV
irol6
5:17
27–1
734,
1991
.(M
edlin
e:91
1627
18)
Not
es:
Dis
ulfid
ebo
ndbe
twee
ncy
stei
nes
and
type
Ire
vers
etu
rnab
out
the
resi
dues
SG
KL
are
stru
ctur
alfe
atur
esof
the
imm
unod
omin
antd
omai
nof
gp41
:CS
GK
LIC
.
[Ors
ini(
1995
)]M
.J.
Ors
ini,
A.
N.
Tha
kur,
W.
W.
And
rew
s,M
.-L.
Ham
-m
arsk
jold
,&
D.
Rek
osh.
Exp
ress
ion
and
Pur
ifica
tion
ofth
eH
IVTy
pe1
Rev
Pro
tein
Pro
duce
din
Esc
heric
hia
coli
and
ItsU
sein
the
Gen
erat
ion
ofM
onoc
lona
lAnt
ibod
ies.A
IDS
Re
sH
um
Re
trov
iru
ses11:9
45–9
53,1
995.
(Med
line:
9602
0095
).
[Orv
ell(
1991
)]C
.O
rvel
l,T.
Ung
e,R
.B
hikh
abha
i,K
.B
ackb
ro,
U.
Rud
en,
B.S
tran
dber
g,B
.Wah
ren,
&E
.M.F
enyo
.Im
mun
olog
ical
char
acte
rizat
ion
ofth
ehu
man
imm
unod
efici
ency
viru
sty
pe1
reve
rse
tran
scrip
tase
prot
ein
byth
eus
eof
mon
oclo
nal
antib
odie
s.JG
en
Viro
l72:
1913
–191
8,19
91.
(Med
line:
9134
1478
).
[Osc
herw
itz(1
999)
]J.
Osc
herw
itz,F
.M.G
otch
,K.B
.Cea
se,&
J.A
.Ber
zof-
sky.
New
insi
ghts
and
appr
oach
esre
gard
ing
B-
and
T-ce
llep
itope
sin
HIV
vacc
ine
desi
gn[In
Pro
cess
Cita
tion]
.AID
S13
Sup
plA:
S16
3–74
,19
99.
(Med
line:
2034
0299
).
[Ota
(199
9)]
A.
Ota
,A
.N
.B
autis
ta,
M.
L.Y
adav
,&
S.
Ued
a.A
nti-P
30-
52m
onoc
lona
lan
tibod
ycr
oss-
reac
ted
toE
nvV
3an
din
hibi
ted
the
vira
lm
ultip
licat
ion
ofH
IV-1
-infe
cted
MT-
4ce
lls.H
ybrid
om
a18:
139–
47,1
999.
(Med
line:
9930
6681
).
[Ota
(199
8)]
A.
Ota
,X
.Li
u,H
.F
ujio
,N
.S
akat
o,&
S.
Ued
a.R
ando
mex
-pr
essi
onof
hum
anim
mun
odefi
cien
cyvi
rus-
1(H
IV-1
)p17
(epi
tope
s)on
the
surf
ace
ofth
eH
IV-1
-infe
cted
cell.H
ybrid
om
a17
:73–
5,19
98.
(Med
line:
9818
3842
).
[Ota
&U
eda(
1998
)]A
.Ota
&S
.Ued
a.E
valu
atio
nof
the
affin
itym
easu
rem
ent
ofan
ti-H
IV-1
p17
mon
oclo
nala
ntib
ody
byB
IAco
re.Hyb
rid
om
a17:
471–
7,19
98.
(Med
line:
9908
9389
).
[Ota
&U
eda(
1999
)]A
.Ota
&S
.Ued
a.In
hibi
tory
mec
hani
smof
anti-
P30
-52
mon
oclo
nala
ntib
ody
agai
nsth
uman
imm
unod
efici
ency
viru
sty
pe1
(HIV
-1)
mul
tiplic
atio
nin
infe
cted
MT-
4ce
lls.H
ybrid
om
a18:
235–
41,1
999.
(Med
-lin
e:99
4022
22).
[Ota
ke(1
994)
]K
.O
take
,Y.
Fuj
ii,Y.
Nis
hino
,Q
.Z
hong
,K
.F
ujin
aga,
M.K
ameo
ka,K
.Ohk
i,&
K.I
kuta
.T
heca
rbox
yl-t
erm
inal
regi
onof
HIV
-1ne
fpr
otei
nis
ace
llsu
rfac
edo
mai
nth
atca
nin
tera
ctw
ithC
D4+
Tce
lls.
JIm
mu
no
l153
:582
6–58
37,
1994
.(M
edlin
e:95
0816
31)
Not
es:
Thi
sst
udy
show
sth
atth
eC
-ter
min
alen
dof
Nef
isac
cess
ible
toA
bs.
Thi
sdo
mai
nco
uld
bind
ina
solu
ble
form
toC
D4+
,uni
nfec
ted
cells
,and
this
inte
ract
ion
isin
hibi
ted
inth
epr
esen
ceof
the
C-t
erm
inal
spec
ific
antib
odie
s.S
yncy
tium
form
atio
nw
asre
duce
dby
thes
eA
bsor
pept
ides
.Abs
coul
dst
ain
IIIB
/M10
,bu
tnot
MN
/M10
,inf
ecte
dce
lls,i
na
mem
bran
eim
mun
ofluo
resc
ence
assa
y.
[Otte
ken
(199
6)]
A.O
tteke
n,P.
L.E
arl,
&B
.Mos
s.F
oldi
ng,a
ssem
bly,
and
in-
trac
ellu
lart
raffi
ckin
gof
the
hum
anim
mun
odefi
cien
cyvi
rus
type
1E
nvel
ope
glyc
opro
tein
anal
yzed
with
mon
oclo
nala
ntib
odie
sre
cogn
izin
gm
atur
atio
nal
inte
rmed
iate
s.JV
irol7
0:34
07–1
5,19
96.
(Med
line:
9621
1471
).
[Otte
ken
(199
2)]
A.O
tteke
n,S
.Nic
k,W
.Ber
gter
,G.V
oss,
A.F
aiss
t,C
.Sta
hl-
Hen
nig,
&G
.Hun
sman
n.Id
entifi
catio
nof
aga
gpr
otei
nep
itope
cons
erve
dam
ong
allf
our
grou
psof
prim
ate
imm
unod
efici
ency
viru
ses
byus
ing
mon
-oc
lona
lant
ibod
ies.J
Ge
nV
irol7
3:27
21–2
724,
1992
.(M
edlin
e:93
0190
29)
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-33
DE
C20
00
Not
es:
Ant
i-SIV
agm
TY
O-7
Mab
sw
ere
obta
ined
byin
trap
erito
neal
imm
u-ni
zatio
nof
mic
e.Tw
ore
acte
dw
ithp1
7an
dth
ree
with
p24.
The
anti-
p24
MA
bsre
cogn
ized
anep
itope
pres
enti
nS
IVag
mT
YO
-7,S
IVag
mT
YO
-5,a
ndH
IV-2
/SIV
mac
.The
anti-
p17
reco
gniz
edan
epito
pepr
esen
tin
SIV
agm
TY
O-
7,S
IVag
mT
YO
-5,
HIV
-2/S
IVm
ac,
SIV
agm
TY
O-1
,H
IV-1
,an
dS
IVm
nd.
Thi
sst
udy
show
sth
atth
em
atrix
prot
ein
expr
esse
sat
leas
tone
high
lyco
n-se
rved
epito
pe.
[Ovo
d(1
992)
]V.
Ovo
d,A
.La
gers
tedt
,A
.R
anki
,F.
O.
Gom
bert
,R
.S
pohn
,M
.Ta
htin
en,
G.
Jung
,&
K.
J.K
rohn
.Im
mun
olog
ical
varia
tion
and
im-
mun
ohis
toch
emic
allo
caliz
atio
nof
HIV
-1N
efde
mon
stra
ted
with
mon
o-cl
onal
antib
odie
s.A
IDS
6:25
–34,
1992
.(M
edlin
e:92
1816
22)
Not
es:
Ten
anti-
Nef
MA
bsw
ere
gene
rate
dan
dm
appe
d.N
efis
expr
esse
din
two
iso-
mor
phic
form
s,an
dw
assh
own
tobe
expr
esse
dm
ainl
yin
the
Gol
gico
mpl
exan
dat
the
nucl
ear
mem
bran
e,bu
tocc
asio
nally
xin
the
nucl
eus,
part
icul
arly
inM
T-4
cells
.
[Pal
(199
2)]
R.
Pal
,F.
diM
arzo
Vero
nese
,B
.C
.N
air,
R.
Rah
man
,G
.H
oke,
S.W
.Mum
baue
r,&
M.G
.Sar
ngad
hara
n.C
hara
cter
izat
ion
ofa
neut
raliz
ing
mon
oclo
nala
ntib
ody
toth
eex
tern
algl
ycop
rote
inof
HIV
-1.
Inte
rviro
log
y86
:86–
93,1
992.
(Med
line:
9318
6358
).
[Pal
ker
(198
7)]
T.J.
Pal
ker,
T.J.
Mat
thew
s,M
.E.C
lark
,G.J
.Cia
ncol
o,R
.R.
Ran
dall,
A.J
.Lan
gloi
s,G
.C.W
hite
,B.S
afei
,R.S
nyde
rman
,D.P
.Bol
og-
nesi
,&B
.F.H
ayne
s.A
cons
erve
dep
itope
atth
eC
OO
Hte
rmin
usof
hum
anim
mun
odefi
cien
cyvi
rus
gp12
0en
velo
pepr
otei
nco
ntai
nsan
imm
unod
om-
inan
tep
itope
.Pro
cN
at
Aca
dS
ciU
SA8
4:24
79–2
483,
1987
.(M
edlin
e:87
1756
97).
[Pap
side
ro(1
988)
]L.
D.
Pap
side
ro,
B.
J.P
oies
z,&
R.
A.
Mon
tagn
a.M
ono-
clon
alA
ntib
ody
Iden
tifies
aH
ighl
yC
onse
rved
and
Imm
unod
omin
ant
Epi
-to
peof
the
Hum
anIm
mun
odefi
cien
cyV
irus
Tra
nsm
embr
ane
Pro
tein
.H
y-b
rid
om
a7:
117–
128,
1988
.(M
edlin
e:88
2266
64).
[Pap
side
ro(1
989)
]L.
D.
Pap
side
ro,
M.
She
u,&
F.W
.R
usce
tti.
Hum
anim
-m
unod
efici
ency
viru
sty
pe1-
neut
raliz
ing
mon
oclo
nala
ntib
odie
sw
hich
reac
tw
ithp1
7co
repr
otei
n:ch
arac
teriz
atio
nan
dep
itope
map
ping
.J
Viro
l63:
267–
272,
1989
.(M
edlin
e:89
0688
40)N
otes
:Tw
oM
abs
with
over
lapp
ing
bind
ing
site
son
p17
redu
ced
the
infe
ctiv
ityof
free
viru
s.A
p24
mon
oclo
nalw
asno
tab
leto
doth
is.
[Par
k(2
000)
]E
.J.
Par
k,M
.K
.G
orny
,S
.Z
olla
-Paz
ner,
&G
.V.
Qui
nnan
.A
glob
alne
utra
lizat
ion
resi
stan
ceph
enot
ype
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
isde
term
ined
bydi
stin
ctm
echa
nism
sm
edia
ting
enha
nced
infe
c-tiv
ityan
dco
nfor
mat
iona
lcha
nge
ofth
een
velo
peco
mpl
ex.
JV
irol7
4:41
83–
91,2
000.
(Med
line:
2021
9411
).
[Par
ker
(199
6)]
C.E
.Par
ker,
D.I
.Pap
ac,S
.K.T
roja
k,&
K.B
.Tom
er.E
pito
pem
appi
ngby
mas
ssp
ectr
omet
ry:d
eter
min
atio
nof
anep
itope
onH
IV-1
IIIB
p26
reco
gniz
edby
am
onoc
lona
lant
ibod
y.JIm
mu
no
l157
:198
–206
,199
6.(M
edlin
e:96
2646
91).
[Par
ren
&B
urto
n(19
97)]
P.W
.Par
ren
&D
.Bur
ton.
Ant
ibod
ies
Aga
inst
HIV
-1fr
omP
hage
Dis
play
Libr
ary:
Map
ping
ofan
Imm
une
Res
pons
ean
dP
rogr
ess
tow
ard
Ant
ivira
lIm
mun
othe
rapy
.Ch
em
Imm
un
ol65
:18–
56,
1997
.(M
ed-
line:
9717
1699
)N
otes
:E
dito
r,J.
D.
Cap
ra.
An
exce
llent
revi
ewof
the
po-
tent
ialf
oran
tivira
lim
mun
eth
erap
yus
ing
anti-
HIV
hum
anm
onoc
lona
lan-
tibod
ies,
emph
asiz
ing
phag
edi
spla
ylib
rary
tech
nolo
gy,
and
appl
icat
ion
toH
IV.F
abs
togp
120
and
gp41
are
sum
mar
ized
.The
met
hodo
logy
ofse
lect
ion
fore
nhan
ced
affin
ityis
disc
usse
d,an
daf
finity
show
nto
bere
late
dto
neut
ral-
izat
ion.
Fab
sex
pres
sed
inph
age
disp
lay
libra
ries
wer
ege
nera
llyco
nver
ted
toIg
Gm
olec
ules
only
ifth
eysh
owne
utra
lizat
ion
pote
ntia
lin
vitr
o,
and
this
conv
ersi
onto
anIg
Gen
hanc
esne
utra
lizin
gpo
tent
ialf
orim
mun
othe
ra-
peut
ics.
The
use
ofph
age
disp
lay
libra
ries
toas
sess
vacc
ines
isdi
scus
sed.
gp12
0,gp
160
and
gp14
0-ol
igom
eric
vacc
ines
wer
eco
mpa
red
asan
tigen
for
sele
ctio
nfr
omph
age
disp
lay
libra
ries.
Des
pite
the
fact
that
CD
4BS
,V3
loop
,and
CD
4BS
-V2
loop
dire
cted
Abs
wer
eob
tain
edin
vacc
inee
s,no
neof
thes
eva
ccin
esef
ficie
ntly
sele
cted
neut
raliz
ing
Abs
from
long
-ter
mas
ymp-
tom
atic
dono
rsin
phag
edi
spla
ylib
rarie
s.T
hepr
otei
nw
ithth
ebe
stpo
tent
ial
usin
gth
ism
etho
dw
asfo
und
tobe
nativ
eol
igom
eric
HIV
-1E
nvel
ope
ex-
pres
sed
onin
fect
edce
lls.T
hepo
ssib
ility
ofus
ing
2G12
,IgG
1b1
2an
d2F
5in
com
bina
tion
for
imm
unot
hera
pyis
disc
usse
d.
[Par
ren
(199
5)]
P.W
.Par
ren,
H.J
.Ditz
el,R
.J.G
uliz
ia,J
.M.B
inle
y,C
.F.B
.3r
d,D
.R
.B
urto
n,&
D.
E.
Mos
ier.
Pro
tect
ion
agai
nst
HIV
-1in
fect
ion
inhu
-PB
L-S
CID
mic
eby
pass
ive
imm
uniz
atio
nw
itha
neut
raliz
ing
hum
anm
onoc
lona
lant
ibod
yag
ains
tth
egp
120
CD
4-bi
ndin
gsi
te.
AID
S9:
F1–
F6,
1995
.(M
edlin
e:95
3911
59)
Not
es:
The
Fab
b12,
at1.
9m
g/kg
,w
asab
leto
prot
ect
25%
ofhu
-PB
L-S
CID
mic
efr
omH
IV-1
infe
ctio
nsh
owin
gth
atco
mpl
ete
prot
ectio
nag
ains
tHIV
-1in
fect
ion
can
beac
hiev
edin
the
hu-P
BL-
SC
IDm
odel
bypa
ssiv
eim
mun
izat
ion
with
phys
iolo
gica
llyre
leva
ntdo
ses
ofan
tibod
y.
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-34
DE
C20
00
[Par
ren
(199
7a)]
P.W
.Par
ren,
M.C
.Gau
duin
,R.A
.Kou
p,P.
Poi
gnar
d,P.
Fis
i-ca
ro,
D.
R.
Bur
ton,
&Q
.J.
Sat
tent
au.
Rel
evan
ceof
the
antib
ody
resp
onse
agai
nst
hum
anim
mun
odefi
cien
cyvi
rus
type
1E
nvel
ope
tova
ccin
ede
sign
[cor
rect
edan
dre
publ
ishe
din
Imm
unol
Lett
1997
Jul;5
8(2)
:125
-32]
.Im
-m
un
olL
ett5
7:10
5–12
,199
7a.
(Med
line:
9737
6324
).
[Par
ren
(199
7b)]
P.W
.Par
ren,
M.C
.Gau
duin
,R.A
.Kou
p,P.
Poi
gnar
d,Q
.J.
Sat
tent
au,P
.Fis
icar
o,&
D.R
.Bur
ton.
Err
atum
toR
elev
ance
ofth
ean
tibod
yre
spon
seag
ains
thum
anim
mun
odefi
cien
cyvi
rus
type
1E
nvel
ope
tova
ccin
ede
sign
[cor
rect
edan
dre
publ
ishe
dar
ticle
orig
inal
lypr
inte
din
Imm
unol
Lett
1997
Jun
1;57
(1-3
):10
5-12
].Imm
un
olL
ett5
8:12
5–32
,19
97b.
(Med
line:
9741
5525
).
[Par
ren
(199
8a)]
P.W
.Par
ren,
I.M
ondo
r,D
.Nan
iche
,H.J
.Ditz
el,P
.J.K
lass
e,D
.R.B
urto
n,&
Q.J
.Sat
tent
au.N
eutr
aliz
atio
nof
hum
anim
mun
odefi
cien
cyvi
rus
type
1by
antib
ody
togp
120
isde
term
ined
prim
arily
byoc
cupa
ncy
ofsi
tes
onth
evi
rion
irres
pect
ive
ofep
itope
spec
ifici
ty.
JV
irol7
2:35
12–9
,19
98a.
(Med
line:
9821
6707
)N
otes
:T
heau
thor
spr
opos
eth
atth
eoc
cu-
panc
yof
bind
ing
site
son
HIV
-1vi
rions
isth
em
ajor
fact
orin
dete
rmin
ing
neut
raliz
atio
n,irr
espe
ctiv
eof
epito
pesp
ecifi
city
.Neu
tral
izat
ion
was
assa
yed
T-ce
ll-lin
e-ad
apte
dH
IV-1
isol
ates
.B
indi
ngof
Fab
sto
mon
omer
icrg
p120
was
notc
orre
late
dw
ithbi
ndin
gto
func
tiona
lolig
omer
icgp
120
orne
utra
l-iz
atio
n,w
hile
bind
ing
tofu
nctio
nalo
ligom
eric
gp12
0w
ashi
ghly
corr
elat
edw
ithne
utra
lizat
ion.
The
ratio
sof
olig
omer
bind
ing/
neut
raliz
atio
nw
ere
sim
-ila
rfor
antib
odie
sto
diffe
rent
neut
raliz
atio
nep
itope
s,w
itha
few
exce
ptio
ns.
[Par
ren
(199
9)]
P.W
.P
arre
n,J.
P.M
oore
,D
.R
.B
urto
n,&
Q.
J.S
atte
ntau
.T
hene
utra
lizin
gan
tibod
yre
spon
seto
HIV
-1:v
irale
vasi
onan
des
cape
from
hum
oral
imm
unity
[InP
roce
ssC
itatio
n].AID
S13
Sup
plA:
S13
7–62
,199
9.(M
edlin
e:20
3402
98).
[Par
ren
(199
8b)]
P.W
.Par
ren,
M.W
ang,
A.T
rkol
a,J.
M.B
inle
y,M
.Pur
tsch
er,
H.K
atin
ger,
J.P.
Moo
re,&
D.R
.Bur
ton.
Ant
ibod
yne
utra
lizat
ion-
resi
stan
tpr
imar
yis
olat
esof
hum
anim
mun
odefi
cien
cyvi
rus
type
1.J
Viro
l72:
1027
0–4,
1998
b.(M
edlin
e:99
0309
46).
[Pee
t(19
98)]
N.
M.
Pee
t,J.
A.
McK
eatin
g,J.
B.
deS
ouza
,I.
M.
Roi
tt,P.
J.D
elve
s,&
T.Lu
nd.
The
effe
ctof
low
-pro
file
serin
esu
bstit
utio
nsin
the
V3
loop
ofH
IV-1
.Viro
log
y25
1:59
–70,
1998
.(M
edlin
e:99
0330
93).
[Pet
rov
(199
0)]
R.V
.Pet
rov,
R.M
.Kha
itov,
I.G
.Sid
orov
ich,
S.P
.Pav
likov
,I.
A.
Nik
olae
va,
M.
E.
Ivac
henk
o,S
.M
.A
ndre
ev,
&L.
Y.U
.S
klya
rov.
The
use
ofsy
nthe
ticpe
ptid
esin
the
diag
nosi
sof
HIV
infe
ctio
ns.
Bio
me
dS
ci1:
239–
244,
1990
.(M
edlin
e:91
3637
60)
Not
es:P
eptid
esfr
om2
regi
ons
ofE
nvw
ere
part
icul
arly
imm
unor
eact
ive
inE
LIS
Ate
sts
with
hum
anse
rafr
omH
IV-1
posi
tive
indi
vidu
als:
495-
516
ofgp
120
(SP
-III)
,pe
ptid
e58
4-60
2of
gp41
(LS
-19)
,an
dpe
ptid
e60
1-61
6of
gp41
(SP
-15)
.U
gand
ase
rare
acte
dw
ithbo
thS
P-I
IIfr
omH
TLV
-III
and
SP
-29
(gp4
1,59
8-60
9)fr
omth
eLA
V-E
LIis
olat
e.H
IV-1
pept
ides
from
gp32
wer
eno
tcro
ss-r
eact
ive.
[Pin
cus
(199
1)]
S.H
.Pin
cus,
R.L
.Col
e,E
.M.H
ersh
,D.L
ake,
Y.M
asuh
o,P.
J.D
urda
,&J.
McC
lure
.In
Vitr
oE
ffica
cyof
Ant
i-HIV
Imm
unot
oxin
sTa
rget
edby
Vario
usA
ntib
odie
sto
the
Env
elop
eP
rote
in.
JIm
mu
no
l146
:431
5–43
24,
1991
.(M
edlin
e:91
2507
25)
Not
es:
Six
MA
bs,
(907
,92
4,11
0.1,
41.1
,86
and
P5-
3)an
dpo
lycl
onal
pool
edse
rum
antib
odie
spu
rified
ongp
160
wer
eco
uple
dto
RA
Cto
crea
teim
mun
otox
ins.
Onl
y41
.1-R
AC
,an
anti-
gp41
MA
b-im
mun
otox
inan
dth
epo
lycl
onal
imm
unot
oxin
show
eddi
rect
activ
ityag
ains
tmul
tiple
stra
ins,
and
activ
ityof
anim
mun
otox
inw
asfo
und
nott
obe
dire
ctly
corr
elat
edw
ithce
llsu
rfac
ebi
ndin
g.
[Pin
cus
(199
8)]
S.
H.
Pin
cus,
R.
L.C
ole,
R.
Wat
son-
McK
own,
A.
Pin
ter,
W.
Hon
nen,
B.
Col
e,&
K.
S.
Wis
e.Im
mun
olog
iccr
oss-
reac
tion
betw
een
HIV
type
1p1
7an
dM
ycop
lasm
ahy
orhi
nis
varia
ble
lipop
rote
in.
AID
SR
es
Hu
mR
etr
oviru
ses1
4:41
9–25
,199
8.(M
edlin
e:98
2068
78).
[Pin
cus
&M
cClu
re(1
993)
]S
.H.P
incu
s&
J.M
cClu
re.S
olub
leC
D4
enha
nces
the
effic
acy
ofim
mun
otox
ins
dire
cted
agai
nst
gp41
ofth
ehu
man
imm
un-
odefi
cien
cyvi
rus.
Pro
cN
atl
Aca
dS
ciU
SA9
0:33
2–6,
1993
.(M
edlin
e:93
1263
70).
[Pin
cus
(199
3)]
S.H
.Pin
cus,
K.G
.Mes
ser,
D.H
.Sch
war
tz,G
.K.L
ewis
,B.S
.G
raha
m,W
.A.B
lattn
er,&
G.F
ishe
r.D
iffer
ence
sin
the
antib
ody
resp
onse
tohu
man
imm
unod
efici
ency
viru
s-1
Env
elop
egl
ycop
rote
in(g
p160
)in
infe
cted
labo
rato
ryw
orke
rsan
dva
ccin
ees.JC
linIn
vest
91:1
987–
96,1
993.
(Med
line:
9325
3041
).
[Pin
cus
(198
9)]
S.
H.
Pin
cus,
K.
Weh
rly,
&B
.C
hese
bro.
Tre
atm
ent
ofH
IVtis
sue
cultu
rein
fect
ion
with
mon
oclo
nala
ntib
ody-
ricin
Ach
ain
conj
ugat
es.
JIm
mu
no
l142
:307
0–30
75,1
989.
(Med
line:
8921
5266
).
[Pin
cus
(199
6)]
S.H
.Pin
cus,
K.W
ehrly
,R.C
ole,
H.F
ang,
G.K
.Lew
is,J
.Mc-
Clu
re,
A.
J.C
onle
y,B
.W
ahre
n,M
.R
.P
osne
r,A
.L.
Not
kins
,S
.A
.T
illey
,A
.Pin
ter,
L.E
iden
,M.T
eint
ze,D
.Dor
war
d,&
V.V.
Tols
tikov
.In
vitr
oef
fect
sof
anti-
HIV
imm
unot
oxin
sdi
rect
edag
ains
tm
ultip
leep
itope
son
HIV
type
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-35
DE
C20
00
1en
velo
pegl
ycop
rote
in16
0.AID
SR
es
Hu
mR
etr
oviru
ses12
:104
1–10
51,
1996
.(M
edlin
e:96
4247
59)
Not
es:
Apa
nel
ofan
ti-gp
160
MA
bsto
was
used
toco
nstr
ucta
nti-H
IVim
mun
otox
ins
byco
uplin
gan
tibod
ies
toric
inA
chai
n(R
AC
).T
heab
ility
ofth
eim
mun
otox
ins
toki
llH
IV-1
-infe
cted
cells
was
test
edin
tissu
ecu
lture
.Im
mun
otox
ins
that
bind
epito
pes
onth
ece
llsu
rfac
eki
lled
infe
cted
cells
,al
thou
ghki
lling
was
not
dire
ctly
prop
ortio
nal
tobi
ndin
g.T
heac
tivity
ofan
ti-gp
41im
mun
otox
ins
was
mar
kedl
yen
hanc
edin
the
pres
ence
ofsC
D4.
[Pin
ter
(199
3a)]
A.P
inte
r,W
.J.H
onne
n,M
.E.R
acho
,&S
.A.T
illey
.Apo
tent
,ne
utra
lizin
ghu
man
mon
oclo
nala
ntib
ody
agai
nsta
uniq
ueep
itope
over
lap-
ping
the
CD
4-bi
ndin
gsi
teof
HIV
-1gp
120
that
isbr
oadl
yco
nser
ved
acro
ssN
orth
Am
eric
anan
dA
fric
anvi
ral
isol
ates
.AID
SR
es
Hu
mR
etr
oviru
ses
9:98
5–99
6,19
93a.
(Med
line:
9410
7600
).
[Pin
ter
(199
3b)]
A.
Pin
ter,
W.
J.H
onne
n,&
S.
A.
Till
ey.
Con
form
atio
nal
chan
ges
affe
ctin
gth
eV
3an
dC
D4-
bind
ing
dom
ains
ofhu
man
imm
unod
efi-
cien
cyvi
rus
type
1gp
120
asso
ciat
edw
ithen
vpr
oces
sing
and
with
bind
ing
oflig
ands
toth
ese
site
s.JV
irol6
7:56
92–5
697,
1993
b.(M
edlin
e:93
3536
54).
[Pin
ter
(198
9)]
A.P
inte
r,W
.J.H
onne
n,S
.A.T
illey
,C.B
ona,
H.Z
agho
uani
,M
.K.G
orny
,&S
.Zol
la-P
azne
r.O
ligom
eric
Str
uctu
reof
gp41
,the
Tra
ns-
mem
bran
eP
rote
inof
Hum
anIm
mun
odefi
cien
cyV
irus
Type
1.JV
irol
63:2
674–
2679
,198
9.(M
edlin
e:89
2590
48).
[Pin
ter
(199
5)]
C.
Pin
ter,
A.
G.
Sic
card
i,&
A.
Cliv
io.
Pro
duct
ion
ofhu
man
imm
unod
efici
ency
viru
sby
chro
nica
llyin
fect
edce
llsgr
own
inpr
otei
n-fr
eem
ediu
m.C
ell
Bio
lIn
t19:
507–
515,
1995
.(M
edlin
e:95
3680
20).
[Piro
fski
(199
3)]
L.-A
.P
irofs
ki,
E.
K.
Tho
mas
,&
M.
D.
Sch
arff.
Varia
ble
regi
onge
neut
iliza
tion
and
mut
atio
nin
agr
oup
ofne
utra
lizin
gm
urin
ean
ti-hu
man
imm
unod
efici
ency
viru
sty
pe1
prin
cipa
lneu
tral
izin
gde
term
inan
tan-
tibod
ies.
AID
SR
es
Hu
mR
etr
oviru
ses9:41
–49,
1993
.(M
edlin
e:93
1522
85)
Not
es:
Obs
erve
dre
stric
ted
subs
etof
mur
ine
Vhe
avy
and
light
chai
nge
neel
emen
tsin
ase
tof5
antib
odie
sth
atbi
ndto
the
tipof
the
V3
loop
.
[Poi
gnar
d(1
996a
)]P.
Poi
gnar
d,T.
Fou
ts,
D.
Nan
iche
,J.
P.M
oore
,&
Q.
J.S
atte
ntau
.N
eutr
aliz
ing
antib
odie
sto
hum
anim
mun
odefi
cien
cyvi
rus
type
-1
gp12
0in
duce
enve
lope
glyc
opro
tein
subu
nit
diss
ocia
tion.JE
xpM
ed
183:
473–
484,
1996
a.(M
edlin
e:96
1952
01)
Not
es:B
indi
ngof
Ant
i-V3
and
the
CD
4Ine
utra
lizin
gM
Abs
indu
ces
shed
ding
ofgp
120
once
llsin
fect
edw
ithth
eT-
cell
line-
adap
ted
HIV
-1m
olec
ular
clon
eH
x10.
Thi
sw
assh
own
bysi
gnifi
cant
incr
ease
sof
gp12
0in
the
supe
rnat
ant,
and
expo
sure
ofa
gp41
epito
peth
atis
mas
ked
inth
eol
igom
er.M
Abs
bind
ing
eith
erto
the
V2
loop
orto
CD
4BS
disc
ontin
uous
epito
pes
dono
tind
uce
gp12
0di
ssoc
iatio
n.T
his
sugg
ests
HIV
neut
raliz
atio
npr
obab
lyis
caus
edby
seve
ralm
echa
nism
s,an
don
eof
the
mec
hani
sms
may
invo
lve
gp12
0di
ssoc
iatio
n.
[Poi
gnar
d(1
996b
)]P.
Poi
gnar
d,P.
J.K
lass
e,&
Q.J
.Sat
tent
au.
Ant
ibod
yne
u-tr
aliz
atio
nof
HIV
-1.
Imm
un
olo
gy
Tod
ay1
7:23
9–24
6,19
96b.
(Med
line:
9710
4961
)N
otes
:Com
preh
ensi
vere
view
ofH
IVen
velo
pegp
120
and
gp41
antib
ody
bind
ing
dom
ains
,an
ddi
ffere
ntcr
oss-
reac
tivity
grou
psof
MA
bsab
ility
tone
utra
lize
prim
ary
isol
ates
.The
dist
inct
ion
betw
een
neut
raliz
atio
nof
labo
rato
ryst
rain
san
dpr
imar
yis
olat
esis
disc
usse
d.T
heon
lyth
ree
epi-
tope
sth
atha
veco
nfirm
edbr
oad
neut
raliz
atio
nag
ains
tasp
ectr
umof
isol
ates
are
gp12
0ep
itope
sfo
rIg
G1b
12an
d2G
12,a
ndth
egp
41ep
itope
of2F
5.
[Poi
gnar
d(1
999)
]P.
Poi
gnar
d,R
.Sab
be,G
.R.P
icch
io,M
.Wan
g,R
.J.G
uliz
ia,
H.
Kat
inge
r,P.
W.
Par
ren,
D.
E.
Mos
ier,
&D
.R
.B
urto
n.N
eutr
aliz
ing
antib
odie
sha
velim
ited
effe
cts
onth
eco
ntro
lofe
stab
lishe
dH
IV-1
infe
ctio
nin
vivo
.Im
mu
nity
10:4
31–8
,199
9.(M
edlin
e:99
2441
92).
[Pol
lock
(198
9)]
B.J
.Pol
lock
,A.S
.McK
enzi
e,B
.E.K
emp,
D.A
.McP
hee,
&A
.J.F
.D’A
pice
.H
uman
mon
oclo
nala
ntib
odie
sto
HIV
-1:c
ross
-rea
ctio
nsw
ithga
gan
den
vpr
otei
ns.Clin
Exp
Imm
un
ol78
:323
–328
,198
9.(M
edlin
e:90
1252
11).
[Pos
ner
(199
2a)]
M.
Pos
ner,
L.C
avac
ini,
C.
Em
es,
J.P
ower
,M
.G
orny
,&
S.
Zol
la-P
azne
r.H
uman
Mon
oclo
nalA
ntib
odie
sto
the
V3
Loop
ofgp
120
Med
iate
Varia
ble
and
Dis
tinct
Effe
cts
onB
indi
ngan
dV
iralN
eutr
aliz
atio
nby
aH
uman
Mon
oclo
nalA
ntib
ody
toth
eC
D4
Bin
ding
Site
.J
Ce
llB
ioch
em
Sup
plO
(16
part
E):6
9,19
92a.
[Pos
ner
(199
3)]
M.R
.Pos
ner,
L.A
.Cav
acin
i,C
.L.E
mes
,J.P
ower
,&R
.Byr
n.N
eutr
aliz
atio
nof
HIV
-1by
F10
5,a
Hum
anM
onoc
lona
lAnt
ibod
yto
the
CD
4B
indi
ngS
iteof
gp12
0.J
AID
S6:
7–14
,199
3.(M
edlin
e:93
1082
53).
[Pos
ner
(199
5)]
M.
R.
Pos
ner,
L.A
.C
avac
ini,
J.G
ambe
rtog
lio,
C.
Spi
no,
E.
Wol
fe,
C.
Tra
pnel
l,N
.K
ette
r,S
.H
amm
er,
&M
.S
amor
e.A
nA
CT
Gph
ase
Iasa
fety
and
phar
mac
okin
etic
tria
lof
imm
unot
hera
pyw
ithth
ean
ti-C
D4
bind
ing
site
hum
anm
onoc
lona
lant
ibod
yF
105.
Na
tlC
on
fHu
mR
etr
o-
viru
ses
Re
latI
nfe
ct(2
nd
)1995
:150
,199
5.N
otes
:Aid
slin
e:95
9205
46A
b-st
ract
:E
ight
HIV
-pos
itive
asym
ptom
atic
indi
vidu
als
wer
egi
ven
F10
5by
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-36
DE
C20
00
intr
aven
ous
infu
sion
.The
rew
ere
nocl
inic
alsi
deef
fect
sor
chan
ges
inbi
o-ch
emic
alte
sts
amon
gth
eei
ghtv
olun
teer
s.T
hepl
asm
aha
lflif
eof
F10
5ha
da
rang
eof
8.7-
18.6
days
.
[Pos
ner
(199
2b)]
M.
R.
Pos
ner,
H.
S.
Elb
oim
,T.
Can
non,
L.C
avic
ini,
&T.
Hid
eshi
ma.
Fun
ctio
nal
Act
ivity
ofan
HIV
-1N
eutr
aliz
ing
IgG
Hum
anM
onoc
lona
lAnt
ibod
y:A
DC
Can
dC
ompl
emen
t-M
edia
ted
Lysi
s.A
IDS
Re
sH
um
Re
trov
iru
ses8:
553–
558,
1992
b.(M
edlin
e:92
3851
56).
[Pos
ner
(199
1)]
M.R
.Pos
ner,
T.H
ides
him
a,T.
Can
non,
M.M
ukhe
rjee,
K.H
.M
ayer
,&
R.
A.
Byr
n.A
nIg
Ghu
man
mon
oclo
nal
antib
ody
that
reac
tsw
ithH
IV-I
/gp1
20,i
nhib
itsvi
rus
bind
ing
toce
lls,a
ndne
utra
lizes
infe
ctio
n.J
Imm
un
ol1
46:4
325–
4332
,19
91.
(Med
line:
9125
0726
)N
otes
:O
rigin
alpa
per
desc
ribin
gth
ene
utra
lizin
gM
Ab
F10
5.
[Pot
ts(1
993)
]B
.J.
Pot
ts,
K.
G.
Fie
ld,
Y.W
u,M
.P
osne
r,L.
Cav
acin
i,&
M.W
hite
-Sch
arf.
Syn
ergi
stic
Inhi
bitio
nof
HIV
-1by
CD
4B
indi
ngD
omai
nR
eage
nts
and
V3-
Dire
cted
Mon
oclo
nalA
ntib
odie
s.V
irolo
gy
197:
415–
419,
1993
.(M
edlin
e:94
0255
92)
Not
es:
Fou
ran
ti-V
3lo
opM
Abs
,(5
9.1,
83.1
,50
.1,
and
58.2
),w
ere
eval
uate
dfo
rth
eir
affin
ity,
neut
raliz
atio
npo
tenc
ies,
and
thei
rab
ility
tosy
nerg
ize
F10
5or
sCD
4ne
utra
lizat
ion.
The
mos
tim
-po
rtan
tpa
ram
eter
for
syne
rgy
was
the
capa
city
tone
utra
lize
agi
ven
viru
sin
depe
nden
tly.
[Pou
mbo
urio
s(1
995)
]P.
Pou
mbo
urio
s,W
.ElA
hmar
,D.A
.McP
hee,
&B
.E.
Kem
p.D
eter
min
ants
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
enve
lope
glyc
opro
tein
olig
omer
icst
ruct
ure.J
Viro
l69:
1209
–121
8,19
95.
(Med
line:
9511
5079
).
[Pou
mbo
urio
s(1
992)
]P.
Pou
mbo
urio
s,D
.A
.M
cPhe
e,&
B.
E.
Kem
p.A
nti-
body
epito
pes
sens
itive
toth
est
ate
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
gp41
olig
omer
izat
ion
map
toa
puta
tive
alph
a-he
lical
regi
on.
AID
SR
es
Hu
mR
etr
oviru
ses8:
2055
–206
2,19
92.
(Med
line:
9315
2279
).
[Pur
tsch
er(1
996)
]M
.P
urts
cher
,A
.T
rkol
a,A
.G
rass
auer
,P.
M.
Sch
ulz,
A.
Klim
a,S
.D
oppe
r,G
.G
rube
r,A
.B
ucha
cher
,T.
Mus
ter,
&H
.K
atin
ger.
Res
tric
ted
antig
enic
varia
bilit
yof
the
epito
pere
cogn
ized
byth
ene
utra
lizin
ggp
41an
tibod
y2F
5.AID
S10
:587
–593
,199
6.(M
edlin
e:96
3745
85)
Not
es:
Bin
ding
and
neut
raliz
atio
nto
gp41
ELD
KW
Ava
riant
sby
anti-
gp41
MA
b2F
5w
ere
stud
ied.
LDK
Wis
the
core
bind
ing
mot
if.
[Pur
tsch
er(1
994)
]M
.Pur
tsch
er,A
.Trk
ola,
G.G
rube
r,A
.Buc
hach
er,R
.Pre
dl,
F.S
tein
dl,
C.
Taue
r,R
.B
erge
r,N
.B
arre
tt,A
.Ju
ngba
uer,
&H
.K
atin
ger.
Abr
oadl
yne
utra
lizin
ghu
man
mon
oclo
nala
ntib
ody
agai
nstg
p41
ofhu
man
imm
unod
efici
ency
viru
sty
pe1.A
IDS
Re
sH
um
Re
trov
iru
ses10:1
651–
1658
,19
94.
(Med
line:
9519
4731
).
[Qia
n&
Tom
er(1
998)
]X
.H
.Q
ian
&K
.B
.To
mer
.A
ffini
tyca
pilla
ryel
ec-
trop
hore
sis
inve
stig
atio
nof
anep
itope
onhu
man
imm
unod
efici
ency
viru
sre
cogn
ized
bya
mon
oclo
nal
antib
ody.E
lect
rop
ho
resi
s19:
415–
9,19
98.
(Med
line:
9821
1519
).
[Ran
ki(1
994)
]A
.Ran
ki,A
.Lag
erst
edt,
V.O
vod,
E.A
avik
,&K
.Kro
hn.
Ex-
pres
sion
kine
tics
and
subc
ellu
lar
loca
lizat
ion
ofH
IV-1
regu
lato
rypr
otei
nsN
efan
dTa
tin
esta
blis
hed
lym
phoi
dce
lllin
es.Arc
hV
irol1
39:3
65–3
78,
1994
.(M
edlin
e:95
1340
92).
[Ran
ki(1
995)
]A
.Ran
ki,M
.Nyb
erg,
V.O
vod,
M.H
altia
,I.E
lova
ara,
R.R
ain-
inko
,H.H
aapa
salo
,&K
.Kro
hn.
Abu
ndan
texp
ress
ion
ofH
IVN
efan
dR
evpr
otei
nsin
brai
nas
troc
ytes
invi
vois
asso
ciat
edw
ithde
men
tia.
AID
S9:
1001
–10
08,1
995.
(Med
line:
9608
5714
)N
otes
:HIV
Nef
prot
ein
was
foun
din
the
brai
nce
llsof
infe
cted
indi
vidu
als
with
clin
ical
neur
olog
ical
dise
ase.
[Rei
tz(1
988)
]M
.S.R
eitz
,C.W
ilson
,C.N
augl
e,&
M.R
ober
t-G
urof
f.G
en-
erat
ion
ofa
neut
raliz
atio
n-re
sist
ant
varia
ntof
HIV
-1is
due
tose
lect
ion
for
apo
int
mut
atio
nin
the
enve
lope
gene
.Ce
ll54
:57–
63,
1988
.(M
edlin
e:88
2534
26)
Not
es:G
row
thof
HX
B2
inth
eco
nsta
ntpr
esen
ceof
ane
utra
liz-
ing
antis
erum
yiel
ded
avi
ralp
opul
atio
nre
sist
ant
toth
esa
me
seru
m.
gp41
mut
atio
n58
2(A
lato
Thr
)co
nfer
red
the
resi
stan
tphe
noty
pe.
[Ric
hard
son
Jr(1
996)
]T.
M.
Ric
hard
son
Jr,
B.
L.S
tryj
ewsk
i,C
.C
.B
rode
r,J.
A.H
oxie
,J.R
.Mas
cola
,P.L
.Ear
l,&
R.W
.Dom
s.H
umor
alre
spon
seto
olig
omer
ichu
man
imm
unod
efici
ency
viru
sty
pe1
enve
lope
prot
ein.
JV
irol
70:7
53–6
2,19
96.
(Med
line:
9613
5183
)N
otes
:A
nE
nvan
tigen
capt
ure
enzy
me-
linke
dim
mun
osor
bent
assa
yus
ing
aso
lubl
e,ol
igom
eric
form
ofH
IV-1
IIIB
Env
(gp1
40)
that
cont
ains
gp12
0an
dth
egp
41ec
todo
mai
nw
asde
velo
ped.
The
gp14
0,ca
ptur
edby
vario
usm
onoc
lona
lant
ibod
ies
(MA
bs),
reta
ined
itsna
tive
olig
omer
icst
ruct
ure:
itbo
und
CD
4an
dw
asre
cogn
ized
byM
Abs
toco
nfor
mat
iona
lepi
tope
sin
gp12
0an
dgp
41,
incl
udin
gol
igom
er-
spec
ific
epito
pes
ingp
41.
[Rin
i(19
93)]
J.M
.Rin
i,E
.A.S
tura
,P.A
.Sal
inas
,A.T
.Pro
fy,&
I.A
.Wils
on.
Cry
stal
stru
ctur
eof
ahu
man
imm
unod
efici
ency
viru
sty
pe1
neut
raliz
ing
antib
ody,
50.1
,in
com
plex
with
itsV
3lo
oppe
ptid
ean
tigen
.P
roc
Na
tlA
cad
Sci
US
A90:
6325
–632
9,19
93.
(Med
line:
9331
7674
)N
otes
:T
heV
3
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-37
DE
C20
00
antig
enic
site
isst
retc
hed
out,
nott
heβtu
rnse
enas
the
prim
ary
dete
rmin
ant
inot
her
publ
ishe
dan
ti-V
3pe
ptid
eF
abst
ruct
ures
.
[Riz
zuto
(199
8)]
C.D
.Riz
zuto
,R.W
yatt,
N.H
erna
ndez
-Ram
os,Y
.Sun
,P.D
.K
won
g,W
.A.H
endr
icks
on,&
J.S
odro
ski.
Aco
nser
ved
HIV
gp12
0gl
yco-
prot
ein
stru
ctur
ein
volv
edin
chem
okin
ere
cept
orbi
ndin
g.S
cie
nce
280:
1949
–53
,19
98.
(Med
line:
9829
6366
)N
otes
:T
his
pape
rco
mpa
res
the
epito
pefo
rC
D4
indu
cibl
eM
Abs
with
the
chem
okin
eco
-rec
epto
rbi
ndin
gsi
teon
the
gp12
0m
olec
ule.
Site
-dire
cted
mut
agen
esis
ofY
U2
Env
was
guid
edby
info
rmat
ion
obta
ined
from
the
crys
talli
zed
CD
4-17
b-gp
120
core
stru
ctur
e,K
won
ge
tal,
1998
.YU
2is
apr
imar
ym
acro
phag
etr
opic
R5
isol
ate
with
high
affin
ityfo
rbo
thC
D4
and
CC
R5.
Apr
otei
nw
ithth
eV
1-V
2lo
ops
dele
ted,
calle
dw
t∆w
asth
eba
sis
for
the
assa
yw
hich
dete
cted
bind
ing
ofvi
rus
toce
llsex
pres
sing
CC
R5
inth
epr
esen
ceof
sCD
4.P
rein
cuba
ton
with
MA
b17
bbl
ocks
bind
ing,
asdi
dth
ena
tura
llig
and
for
CC
R5,
MIP
-1β
and
anti-
CC
R5
MA
b2D
7.M
utat
ions
437
P/A
and
442
Q/L
incr
ease
dC
CR
5bi
ndin
gaf
fin-
ity.T
here
gion
ofgp
120
CC
R5
bind
ing
issh
own
tobe
the
high
lyco
nser
ved
β-s
heet
brid
ging
stru
ctur
e,lo
cate
dpr
oxim
alto
the
V3
loop
.
[Rob
en(1
994)
]P.
Rob
en,J
.P.M
oore
,M.T
hali,
J.S
odro
ski,
C.F
.Bar
bas
III,
&D
.R.B
urto
n.R
ecog
nitio
nP
rope
rtie
sof
aP
anel
ofH
uman
Rec
ombi
nant
Fab
frag
men
tsto
the
CD
4bi
ndin
gsi
teof
gp12
0th
atsh
owdi
fferin
gab
ilitie
sto
neut
raliz
ehu
man
imm
unod
efici
ency
viru
sty
pe1.JV
irol6
8:48
21–4
828,
1994
.(M
edlin
e:94
3091
44).
[Rob
ert-
Gur
off(
1994
)]M
.R
ober
t-G
urof
f,A
.Lo
uie,
M.
Mya
gkik
h,F.
Mic
hael
s,M
.P.
Kie
ny,
M.
E.
Whi
te-S
char
f,B
.P
otts
,D
.G
rogg
,&
M.
S.
Rei
tz.
Alte
ratio
nof
V3
loop
cont
ext
with
inth
een
velo
peof
hum
anim
mun
odefi
cien
cyvi
rus
type
1en
hanc
esne
utra
liza-
tion.
JV
irol
68:3
459–
3466
,19
94.
(Med
line:
9424
6688
)N
otes
:M
N-V
3lo
opin
sert
edin
toa
HB
X2
back
grou
ndre
sults
inen
hanc
edne
utra
lizat
ion
ofan
ti-M
NV
3M
Ab
50.1
and
hum
anH
IV+
sera
whe
nth
ech
imer
icvi
rus
was
com
pare
dto
MN
.Enh
ance
daf
finity
,and
grea
ter
prop
ortio
nsof
labe
led
infe
cted
H9
cells
byFA
CS
anal
ysis
,wer
eal
soob
serv
edus
ing
two
anti-
MN
V3
MA
bs,5
0.1
and
83.1
.
[Rob
ert-
Heb
man
n(1
992a
)]V.
Rob
ert-
Heb
man
n,S
.E
mili
ani,
F.Je
an,
M.R
esni
coff,
&C
.Dev
aux.
Clo
nala
naly
sis
ofm
urin
eB
-cel
lres
pons
eto
the
hum
anim
mun
odefi
cien
cyvi
rus
type
1(H
IV-1
)-ga
gp1
7an
dp2
5an
tigen
s.M
olI
mm
un
ol2
9:72
9–73
8,19
92a.
(Med
line:
9229
3165
).
[Rob
ert-
Heb
man
n(1
992b
)]V.
Rob
ert-
Heb
man
n,S
.E
mili
ani,
M.
Res
nico
ff,F.
Jean
,&C
.Dev
aux.
Sub
typi
ngof
hum
anim
mun
odefi
cien
cyvi
rus
isol
ates
with
apa
nelo
fm
onoc
lona
lant
ibod
ies:
iden
tifica
tion
ofco
nser
ved
and
di-
verg
ente
pito
pes
onp1
7an
dp2
5co
repr
otei
ns.
Mo
lIm
mu
no
l29:
1175
–118
3,19
92b.
(Med
line:
9240
8665
).
[Rob
inso
n(1
992)
]J.
Rob
inso
n,H
.Yo
shiy
ama,
D.
Hol
ton,
S.
Elli
ot,
&D
.D
.H
o.D
istin
ctan
tigen
icsi
tes
onH
IVgp
120
iden
tified
bya
pane
lof
hum
anm
onoc
lona
lant
ibod
ies.J
Ce
llB
ioch
em
Sup
pl16
E:71
,199
2.
[Rob
inso
n(1
990a
)]J.
E.
Rob
inso
n,D
.H
olto
n,S
.P
ache
co-M
orel
l,J.
Liu,
&H
.M
cMur
do.
Iden
tifica
tion
ofco
nser
ved
and
varia
ble
epito
pes
ofhu
man
imm
unod
efici
ency
viru
sty
pe-1
(HIV
-1)
gp12
0by
hum
anm
onoc
lona
lant
i-bo
dies
prod
uced
byE
BV
tran
sfor
med
cell
lines
.A
IDS
Re
sH
um
Re
trov
iru
ses
6:56
7–57
9,19
90a.
(Med
line:
9029
8073
).
[Rob
inso
n(1
991)
]W
.E.R
obin
son,
M.K
.Gor
ny,J
.-Y.
Xu,
W.M
.Mitc
hell,
&S
.Zol
la-P
azne
r.Tw
oIm
mun
odom
inan
tDom
ains
ofgp
41B
ind
Ant
ibod
ies
Whi
chE
nhan
ceH
uman
Imm
unod
efici
ency
Viru
sTy
pe1
Infe
ctio
nIn
Vitr
o.J
Viro
l65:
4169
–417
6,19
91.
(Med
line:
9130
3668
).
[Rob
inso
n(1
990b
)]W
.E
.R
obin
son,
T.K
awam
ura,
M.
K.
Gor
ny,
D.
Lake
,J.
-Y.
Xu,
Y.M
atsu
mot
o,T.
Sug
ano,
Y.M
asuh
o,W
.M
.M
itche
ll,E
.H
ersh
,&
S.Z
olla
-Paz
ner.
Hum
anm
onoc
lona
lant
ibod
ies
toth
ehu
man
imm
unod
-efi
cien
cyvi
rus
type
1(H
IV-1
)tr
ansm
embr
ane
glyc
opro
tein
gp41
enha
nce
HIV
-1in
fect
ion
invi
tro.
Pro
cN
atl
Aca
dS
ciU
SA8
7:31
85–3
189,
1990
b.(M
edlin
e:90
2221
94)N
otes
:Thr
eegp
41M
Abs
outo
f16
Env
and
Gag
MA
bste
sted
enha
nced
HIV
-1III
Bin
fect
ion
ofM
T-2
cells
.The
enha
ncin
gan
tibod
-ie
sw
ere
com
petit
ive
with
the
imm
unod
omin
ante
pito
pes
ofgp
41re
cogn
ized
byse
rafr
omH
IV-1
infe
cted
subj
ects
.
[Rov
insk
i(19
95)]
B.R
ovin
ski,
L.R
odrig
ues,
S.X
.Cao
,F.L
.Yao
,U.M
cGui
n-ne
ss,C
.Sia
,G.C
ates
,S.Z
olla
-Paz
ner,
S.K
arw
owsk
a,T.
J.M
atth
ews,
C.B
.M
cDan
al,
J.M
asco
la,
&M
.H
.K
lein
.In
duct
ion
ofH
IVty
pe1
neut
ral-
izin
gan
den
v-C
D4
bloc
king
antib
odie
sby
imm
uniz
atio
nw
ithge
netic
ally
engi
neer
edH
IVty
pe1-
like
part
icle
sco
ntai
ning
unpr
oces
sed
gp16
0gl
y-co
prot
eins
.AID
SR
es
Hu
mR
etr
oviru
ses11
:118
7–11
95,
1995
.(M
edlin
e:96
1572
06).
[Saa
rloos
(199
5)]
M.N
.Saa
rloos
,T.F
.Lin
t,&
G.T
.Spe
ar.
Effi
cacy
ofH
IV-
spec
ific
and
’ant
ibod
y-in
depe
nden
t’m
echa
nism
sfo
rcom
plem
enta
ctiv
atio
nby
HIV
-infe
cted
cells
.C
linE
xpIm
mu
no
l99:
189–
195,
1995
.(M
edlin
e:95
1539
00).
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-38
DE
C20
00
[Saf
rit(1
993)
]J.
T.S
afrit
,M.S
.C.F
ung,
C.A
.And
rew
s,D
.G.B
raun
,W.N
.C.
Sun
,T.W
.Cha
ng,&
R.A
.Kou
p.hu
-PB
L-S
CID
mic
eca
nbe
prot
ecte
dfr
omH
IV-1
infe
ctio
nby
pass
ive
tran
sfer
ofm
onoc
lona
lant
ibod
yto
the
prin
cipa
lne
utra
lizin
gde
term
inan
tofe
nvel
ope
gp12
0.AID
S7:
15–2
1,19
93.(
Med
line:
9318
3427
).
[Sai
to(1
994)
]Y.
Sai
to,
L.S
hare
r,L.
Eps
tein
,.O
vere
xpre
ssio
nof
Nef
asa
mar
ker
for
rest
ricte
dH
IV-1
infe
ctio
nof
astr
ocyt
esin
post
mor
tem
pedi
atric
cent
raln
ervo
ustis
sues
.N
eu
rolo
gy4
4:47
4–48
1,19
94.(
Med
line:
9419
5501
).
[Sak
aida
(199
7)]
H.
Sak
aida
,T.
Mur
akam
i,S
.K
awam
ata,
T.H
atto
ri,&
T.U
chiy
ama.
V3
loop
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
supp
ress
esin
terle
ukin
2-in
duce
dT
cell
grow
th.AID
SR
es
Hu
mR
etr
oviru
ses13
:151
–9,
1997
.(M
edlin
e:97
1596
84)
Not
es:
See
com
men
tsin
AID
SR
esH
umR
etro
viru
ses
13:6
33(1
997)
.
[Sal
zwed
el(2
000)
]K
.S
alzw
edel
,E
.D
.S
mith
,B
.D
ey,
&E
.A
.B
erge
r.S
e-qu
entia
lCD
4-co
rece
ptor
inte
ract
ions
inhu
man
imm
unod
efici
ency
viru
sty
pe1
Env
func
tion:
solu
ble
CD
4ac
tivat
esE
nvfo
rco
rece
ptor
-dep
ende
ntfu
sion
and
reve
als
bloc
king
activ
ities
ofan
tibod
ies
agai
nst
cryp
ticco
nser
ved
epi-
tope
son
gp12
0.JV
irol7
4:32
6–33
,200
0.(M
edlin
e:20
0579
26).
[Sas
aki(
1998
)]S
.S
asak
i,K
.S
umin
o,K
.H
amaj
ima,
J.F
ukus
him
a,N
.Is
hii,
S.K
awam
oto,
H.M
ohri,
C.R
.Ken
sil,
&K
.Oku
da.
Indu
ctio
nof
syst
emic
and
muc
osal
imm
une
resp
onse
sto
hum
anim
mun
odefi
cien
cyvi
rus
type
1by
aD
NA
vacc
ine
form
ulat
edw
ithQ
S-2
1sa
poni
nad
juva
ntvi
ain
tram
uscu
lar
and
intr
anas
alro
utes
.JV
irol7
2:49
31–9
,199
8.(M
edlin
e:98
2417
32).
[Sat
tent
au(1
995)
]Q
.J.S
atte
ntau
.C
onse
rvat
ion
ofH
IV-1
gp12
0ne
utra
lizin
gep
itope
saf
ter
form
alin
inac
tivat
ion.A
IDS
9:13
83–1
385,
1995
.(M
edlin
e:96
1883
19).
[Sat
tent
au(1
996)
]Q
.J.S
atte
ntau
.N
eutr
aliz
atio
nof
HIV
-1by
antib
ody.
Cu
rrO
pin
inIm
mu
no
l8:5
40–5
45,1
996.
(Med
line:
9639
1802
)N
otes
:Rev
iew
.
[Sat
tent
au&
Moo
re(1
991)
]Q
.J.
Sat
tent
au&
J.P.
Moo
re.
Con
form
atio
nal
chan
ges
indu
ced
inth
ehu
man
imm
unod
efici
ency
viru
sen
velo
pegl
ycop
ro-
tein
byso
lubl
eC
D4
bind
ing.
JE
xpM
ed1
74:4
07–4
15,
1991
.(M
edlin
e:91
3113
00)
Not
es:s
CD
4bi
ndin
gto
gp12
0in
duce
sco
nfor
mat
iona
lcha
nges
with
inen
velo
peol
igom
ers.
Thi
sw
asm
easu
red
onH
IV-1
-infe
cted
cells
byth
ein
crea
sed
bind
ing
ofgp
120/
V3
loop
spec
ific
MA
bs,a
ndon
the
surf
ace
ofvi
rions
byin
crea
sed
clea
vage
ofth
eV
3lo
opby
anex
ogen
ous
prot
eina
se.[S
atte
ntau
&M
oore
(199
5)]
Q.J
.Sat
tent
au&
J.P.
Moo
re.
Hum
anim
mun
od-
efici
ency
viru
sty
pe1
neut
raliz
atio
nis
dete
rmin
edby
epito
peex
posu
reon
the
gp12
0ol
igom
er.J
Exp
Me
d182
:185
–196
,199
5.(M
edlin
e:95
3108
50)
Not
es:T
his
stud
ysu
gges
tsth
atan
tibod
ies
spec
ific
for
one
offiv
edi
ffere
ntbi
ndin
gre
gion
son
gp12
0ar
eas
soci
ated
with
vira
lneu
tral
izat
ion:
V2,
V3,
C4,
the
CD
4bi
ndin
gsi
te,
and
aco
mpl
exdi
scon
tinuo
usep
itope
that
does
noti
nter
fere
with
CD
4bi
ndin
g.K
inet
icbi
ndin
gpr
oper
ties
ofa
seto
fMA
bsth
atbi
ndto
thes
ere
gion
sw
ere
stud
ied,
anal
yzin
gbi
ndin
gto
both
func
tiona
lol
igom
eric
LAI
gp12
0an
dso
lubl
em
onom
eric
LAI
BH
10gp
120;
neut
ral-
izat
ion
ID50s
wer
eal
soev
alua
ted.
Itw
asfo
und
that
the
neut
raliz
atio
nID
50s
was
rela
ted
toth
eab
ility
tobi
ndol
igom
eric
,no
tm
onom
eric
,gp
120,
and
conc
lude
dth
atw
ithth
eex
cept
ion
ofth
eV
3lo
op,r
egio
nsof
gp12
0th
atar
eim
mun
ogen
icw
illbe
poor
lypr
esen
ted
once
ll-lin
e-ad
apte
dvi
rions
.Fur
ther
,th
eas
soci
atio
nra
te,
estim
ated
asth
et
1/2
tore
ach
equi
libriu
mbi
ndin
gto
mul
timer
ic,v
irion
asso
ciat
ed,g
p120
,app
ears
tobe
am
ajor
fact
orre
latin
gto
affin
ityan
dpo
tenc
yof
the
neut
raliz
atio
nre
spon
seto
cell-
line-
adap
ted
viru
s.
[Sat
tent
au(1
993)
]Q
.J.
Sat
tent
au,
J.P.
Moo
re,
F.V
igna
ux,
F.T
rain
card
,&
P.P
oign
ard.
Con
form
atio
nalc
hang
esin
duce
din
the
enve
lope
glyc
opro
tein
sof
the
hum
anan
dsi
mia
nim
mun
odefi
cien
cyvi
ruse
sby
solu
ble
rece
ptor
bind
ing.
JV
irol6
7:73
83–7
393,
1993
.(M
edlin
e:94
0473
53).
[Sat
tent
au(1
995)
]Q
.J.S
atte
ntau
,S.Z
olla
-Paz
ner,
&P.
Poi
gnar
d.E
pito
peex
-po
sure
onfu
nctio
nal,
olig
omer
icH
IV-1
gp41
mol
ecul
es.
Viro
log
y20
6:71
3–71
7,19
95.
(Med
line:
9513
3216
)N
otes
:M
ost
gp41
epito
pes
are
mas
ked
whe
nas
soci
ated
with
gp12
0on
the
cell
surf
ace.
Wea
kbi
ndin
gof
anti-
gp41
MA
bsca
nbe
enha
nced
bytr
eatm
entw
ithsC
D4.
MA
b2F
5bi
nds
toa
mem
-br
ane
prox
imal
epito
pew
hich
bind
sin
the
pres
ence
ofgp
120
with
outs
CD
4.
[Sch
effe
l(19
99)]
J.W
.Sch
effe
l,R
.Zie
man
n,D
.Haw
ksw
orth
,J.T
yner
,R.K
.H
ickm
an,&
J.H
acke
tt.M
onoc
lona
lant
ibod
ies
toan
HIV
-1gr
oup
Oen
ve-
lope
reco
mbi
nant
.JA
cqu
irIm
mu
ne
De
ficS
ynd
r22:2
21–7
,199
9.(M
edlin
e:20
2311
10).
[Sch
neid
er(1
991)
]T.
Sch
neid
er,
H.-
P.H
arth
us,
P.H
elde
bran
dt,
M.
Nie
drig
,M
.B
roke
r,W
.W
eige
lt,A
.B
eck,
&G
.P
auli.
Epi
tope
sof
the
HIV
-1-
nega
tive
fact
orre
activ
ew
ithm
urin
em
onoc
lona
lant
ibod
ies
and
hum
anH
IV-
1-po
sitiv
ese
ra.A
IDS
Re
sH
um
Re
trov
iru
ses7:37
–43,
1991
.(M
edlin
e:91
1975
64)
Not
es:E
pito
pes
for
9m
urin
eM
Abs
wer
em
appe
d,an
dfo
und
tobe
loca
ted
in4
imm
unog
enic
regi
ons.
7/10
sera
from
HIV
-1po
sitiv
ein
di-
vidu
als
reac
ted
toth
efo
urne
fim
mun
ogen
icre
gion
s.
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-39
DE
C20
00
[Sch
onni
ng(1
998)
]K
.S
chon
ning
,A
.B
olm
sted
t,J.
Nov
otny
,O
.S
.Lu
nd,
S.
Olo
fsso
n,&
J.E
.H
anse
n.In
duct
ion
ofan
tibod
ies
agai
nst
epito
pes
inac
cess
ible
onth
eH
IVty
pe1
enve
lope
olig
omer
byim
mun
izat
ion
with
reco
mbi
nant
mon
omer
icgl
ycop
rote
in12
0.AID
SR
es
Hu
mR
etr
oviru
ses
14:1
451–
6,19
98.
(Med
line:
9903
9929
).
[Sch
onni
ng(1
999)
]K
.Sch
onni
ng,O
.Lun
d,O
.S.L
und,
&J.
E.H
anse
n.S
to-
ichi
omet
ryof
mon
oclo
nala
ntib
ody
neut
raliz
atio
nof
T-ce
lllin
e-ad
apte
dhu
-m
anim
mun
odefi
cien
cyvi
rus
type
1.JV
irol7
3:83
64–7
0,19
99.
(Med
line:
9941
2352
).
[Sch
utte
n(1
995a
)]M
.Sch
utte
n,A
.C.A
ndew
eg,M
.L.B
osch
,&A
.D.O
ster
-ha
us.
Enh
ance
men
tof
Infe
ctiv
ityof
aN
on-S
yncy
tium
Indu
cing
HIV
-1by
sCD
4an
dby
Hum
anA
ntib
odie
sth
atN
eutr
aliz
eS
yncy
tium
Indu
cing
HIV
-1.
Sca
nd
JIm
mu
no
l41:1
8–22
,199
5a.
(Med
line:
9512
5392
).
[Sch
utte
n(1
997)
]M
.Sch
utte
n,A
.C.A
ndew
eg,G
.F.R
imm
elzw
aan,
&A
.D.
Ost
erha
us.
Mod
ulat
ion
ofpr
imar
yhu
man
imm
unod
efici
ency
viru
sty
pe1
enve
lope
glyc
opro
tein
-med
iate
den
try
byhu
man
antib
odie
s.J
Ge
nV
irol
78:9
99–1
006,
1997
.(M
edlin
e:97
2969
47)
Not
es:
Ase
ries
ofH
IV-1
enve
-lo
pegl
ycop
rote
ins
from
rela
ted
prim
ary
viru
sis
olat
esof
diffe
rent
SIp
heno
-ty
pes,
toge
ther
with
chim
eras
ofth
ese
prot
eins
,w
ere
test
edin
anen
velo
petr
ans-
com
plem
enta
tion
assa
yfo
rth
eir
sens
itivi
tyto
eith
eran
tibod
ym
edi-
ated
inhi
bitio
nor
enha
ncem
ento
fHIV
-1en
try.
Inco
ntra
stto
the
inhi
bitio
nof
HIV
-1en
try,
antib
ody
med
iate
den
hanc
emen
twas
nott
empe
ratu
rede
pen-
dent
and
coul
dno
tbe
med
iate
dby
F(a
b)fr
agm
ents
,im
plic
atin
gcr
oss-
linki
ngas
anim
port
ant
step
.E
nhan
cem
ent
orin
hibi
tion
seem
edto
bede
term
ined
byvi
rus
isol
ate
rath
erth
anby
the
spec
ifici
tyof
the
antis
erum
used
.2F
5w
asth
eon
lyM
Ab
that
inhi
bite
dth
een
try
ofal
lviru
ses.
[Sch
utte
n(1
995b
)]M
.Sch
utte
n,J.
P.La
nged
ijk,A
.C.A
ndew
eg,R
.C.H
uis-
man
,R.H
.Mel
oen,
&A
.D.O
ster
haus
.C
hara
cter
izat
ion
ofa
V3
dom
ain-
spec
ific
neut
raliz
ing
hum
anm
onoc
lona
lan
tibod
yth
atpr
efer
entia
llyre
c-og
nize
sno
n-sy
ncyt
ium
-indu
cing
hum
anim
mun
odefi
cien
cyvi
rus
type
1st
rain
s.J
Ge
nV
irol7
6:16
65–1
673,
1995
b.(M
edlin
e:90
4937
2)N
otes
:C
hara
cter
izat
ion
ofH
uMA
bM
N21
5.
[Sch
utte
n(1
993)
]M
.Sch
utte
n,A
.McK
nigh
t,R
.C.H
uism
an,M
.Tha
li,J.
A.
McK
eatin
g,J.
Sod
rosk
i,J.
Gou
dsm
it,&
A.
D.
Ost
erha
us.
Fur
ther
char
-ac
teriz
atio
nof
anan
tigen
icsi
teof
HIV
-1gp
120
reco
gniz
edby
viru
sne
u-tr
aliz
ing
hum
anm
onoc
lona
lant
ibod
ies.AID
S7:
919–
923,
1993
.(M
edlin
e:
9336
3254
)N
otes
:Thr
eehu
man
anti-
CD
4bi
ndin
gsi
teM
Abs
wer
ech
arac
-te
rized
.Am
ino
acid
subs
titut
ions
that
bloc
kM
Ab
bind
ing
wer
esi
mila
rbu
tsl
ight
lydi
ffere
ntth
anth
ose
foun
din
mur
ine
anti-
CD
4bi
ndin
gsi
teM
Abs
.
[Sch
utte
n(1
996)
]M
.Sch
utte
n,K
.Ten
ner-
Rac
z,P.
Rac
z,D
.W.v
anB
ekku
m,
&A
.D
.O
ster
haus
.H
uman
antib
odie
sth
atne
utra
lize
prim
ary
hum
anim
-m
unod
efici
ency
viru
sty
pe1
invi
tro
dono
tpro
vide
prot
ectio
nin
aninvi
vom
od
el.J
Ge
nV
irol7
7:16
67–1
675,
1996
.(M
edlin
e:96
3325
03).
[Sco
ttJr
(199
0)]
C.F
.Sco
ttJr
,S.S
ilver
,A.T
.Pro
fy,S
.D.P
utne
y,A
.Lan
gloi
s,K
.Wei
nhol
d,&
J.E
.Rob
inso
n.H
uman
mon
oclo
nala
ntib
ody
that
reco
gniz
esth
eV
3re
gion
ofhu
man
imm
unod
efici
ency
viru
sgp
120
and
neut
raliz
esth
ehu
man
T-ly
mph
otro
pic
viru
sty
peIII
MN
stra
in.P
roc
Na
tlA
cad
Sci
US
A87
:859
7–86
01,1
990.
(Med
line:
9104
6042
).
[Sel
igm
an(1
996)
]S
.J.
Sel
igm
an,
J.M
.B
inle
y,M
.K
.G
orny
,D
.R
.B
urto
n,S
.Z
olla
-Paz
ner,
&K
.A
.S
okol
owsk
i.C
hara
cter
izat
ion
byse
riald
elet
ion
com
petit
ion
ELI
SA
sof
HIV
-1V
3lo
opep
itope
sre
cogn
ized
bym
onoc
lona
lan
tibod
ies.
Mo
lIm
mu
no
l33:
737–
745,
1996
.(M
edlin
e:96
4069
82).
[Sha
fferm
an(1
989)
]A
.S
haffe
rman
,J.
Lenn
ox,
H.
Gro
sfel
d,J.
Sad
off,
R.
R.
Red
field
,&D
.S.B
urke
.P
atte
rns
ofan
tibod
yre
cogn
ition
ofse
lect
edco
n-se
rved
amin
oac
idse
quen
ces
from
the
HIV
enve
lope
inse
rafr
omdi
ffere
ntst
ages
ofH
IVin
fect
ion.A
IDS
Re
sH
um
Re
trov
iru
ses5:33
–39,
1989
.(M
ed-
line:
8924
7164
).
[Sha
ng(1
991)
]F.
Sha
ng,H
.Hua
ng,K
.Rev
esz,
H.-
C.C
hen,
R.H
erz,
&A
.Pin
-te
r.C
hara
cter
izat
ion
ofm
onoc
lona
lant
ibod
ies
agai
nst
the
hum
anim
mun
-od
efici
ency
viru
sm
atrix
prot
ein,
p17g
ag:i
dent
ifica
tion
ofep
itope
sex
pose
dat
the
surf
aces
ofin
fect
edce
lls.JV
irol
65:4
798–
4804
,19
91.
(Med
line:
9133
3022
)N
otes
:Six
MA
bsw
ithlin
ear
epito
pes
wer
em
appe
d.T
hese
Abs
coul
don
lybi
ndto
HIV
-infe
cted
cells
that
had
been
perm
eabl
ized
with
ace-
tone
.Onl
yG
11g1
and
G11
h3,t
wo
antib
odie
sth
atdi
dno
tbin
dto
pept
ides
,bu
ton
lyto
inta
ctp1
7,co
uld
reac
tw
ithliv
eH
IV-1
infe
cted
cells
.T
hese
antib
odie
sw
ere
notn
eutr
aliz
ing.
[Shi
bata
(199
9)]
R.
Shi
bata
,T.
Igar
ashi
,N
.H
aigw
ood,
A.
Buc
kler
-Whi
te,
R.
Oge
rt,
W.
Ros
s,R
.W
illey
,M
.C
ho,
&M
.M
artin
.N
eutr
aliz
ing
anti-
body
dire
cted
agai
nstt
heH
IV-1
enve
lope
glyc
opro
tein
can
com
plet
ely
bloc
kH
IV-1
/SIV
chim
eric
infe
ctio
nsof
mac
aque
sm
onke
ys.
Na
tMe
d5:2
04–2
10,
1999
.(M
edlin
e:99
1280
59).
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-40
DE
C20
00
[Shi
ver
(199
7)]
J.W
.S
hive
r,M
.E
.D
avie
s,Y.
Yas
utom
i,H
.C
.P
erry
,D
.C
.F
reed
,N
.L.
Letv
in,
&M
.A
.Li
u.A
nti-H
IVen
vim
mun
ities
elic
ited
bynu
clei
cac
idva
ccin
es.Va
ccin
e15:
884–
7,19
97.
(Med
line:
9737
8942
).
[Sho
tton
(199
5)]
C.
Sho
tton,
C.
Arn
old,
Q.
Sat
tent
au,
J.S
odro
ski,
&J.
A.
McK
eatin
g.Id
entifi
catio
nan
dch
arac
teriz
atio
nof
mon
oclo
nal
antib
odie
ssp
ecifi
cfo
rpo
lym
orph
ican
tigen
icde
term
inan
tsw
ithin
the
V2
regi
onof
the
hum
anim
mun
odefi
cien
cyvi
rus
type
1en
velo
pegl
ycop
rote
in.
JV
irol
69:2
22–2
30,
1995
.(M
edlin
e:95
0748
68)
Not
es:
Ant
i-V2
linea
ran
dco
n-fo
rmat
ion
depe
nden
tM
Abs
wer
est
udie
d.A
llV
2A
bsst
udie
dco
uld
bind
IIIB
,but
faile
dto
neut
raliz
eno
n-cl
onal
stoc
ks.E
pito
peex
posu
reis
diffe
rent
inrg
p120
com
pare
dto
nativ
egp
120.
HX
B2
V2-
MA
bne
utra
lizat
ion
esca
pem
utan
tsw
ere
sequ
ence
d.
[Sid
orov
a(19
99)]
E.
Sid
orov
a.H
uman
mon
oclo
nal
antib
odie
sto
MN
-24
pept
ide
ofgp
120
HIV
-1.H
um
An
tibo
die
s9:1
07–1
0,19
99.
(Med
line:
9933
4303
).
[Ski
nner
(198
8a)]
M.
A.
Ski
nner
,A
.J.
Lang
lois
,C
.B
.M
cDan
al,
J.S
.M
c-D
ouga
l,D
.P.
Bol
ogne
si,
&T.
J.M
atth
ews.
Neu
tral
izin
gA
ntib
odie
sto
anIm
mun
odom
inan
tE
nvel
ope
Seq
uenc
eD
oN
otP
reve
ntgp
120
Bin
ding
toC
D4.
JV
irol6
2:41
95–4
200,
1988
a.(M
edlin
e:89
0121
92)
Not
es:
Thi
sre
-po
rtw
asan
early
sugg
estio
nth
atth
ere
are
atle
astt
wo
clas
ses
ofbi
olog
ical
lyac
tive
antib
odie
sto
HIV
:one
clas
sis
isol
ate
rest
ricte
d,pr
imar
ilydi
rect
edto
ahy
perv
aria
ble
loop
stru
ctur
eof
gp12
0an
dno
tin
volv
edin
CD
4bi
ndin
g;th
ese
cond
clas
sis
dire
cted
atm
ore
cons
erve
dst
ruct
ures
that
may
dire
ctly
bloc
kC
D4
bind
ing.
[Ski
nner
(198
8b)]
M.A
.Ski
nner
,R.T
ing,
A.J
.Lan
gloi
s,K
.J.W
einh
old,
H.K
.Ly
erly
,K
.Ja
vahe
rian,
&T.
J.M
atth
ews.
Cha
ract
eris
tics
ofa
neut
raliz
ing
mon
oclo
nal
antib
ody
toth
eH
IVen
velo
pegl
ycop
rote
in.
AID
SR
es
Hu
mR
etr
oviru
ses4
:187
–197
,198
8b.
(Med
line:
8828
1280
).
[Sm
ith(1
998)
]A
.D.S
mith
,S.C
.Gei
sler
,A.A
.Che
n,D
.A.R
esni
ck,B
.M.
Roy
,P.J
.Lew
i,E
.Arn
old,
&G
.F.A
rnol
d.H
uman
rhin
oviru
sty
pe14
:hum
anim
mun
odefi
cien
cyvi
rus
type
1(H
IV-1
)V
3lo
opch
imer
asfr
oma
com
bina
-to
riall
ibra
ryin
duce
pote
ntne
utra
lizin
gan
tibod
yre
spon
ses
agai
nst
HIV
-1.
JV
irol7
2:65
1–9,
1998
.(M
edlin
e:98
0804
59)
Not
es:T
hetip
ofth
eM
NV
3lo
op,I
GP
GR
AF
YT
TK
N,w
asin
sert
edin
toco
ld-c
ausi
nghu
man
rhin
oviru
s14
(HR
V14
)an
dch
imer
asw
ere
imm
unos
elec
ted
usin
gM
Abs
447-
52-D
,69
4/98
-D,
NM
-01,
and
59.1
,fo
rgo
odpr
esen
tatio
nof
the
V3
antig
enic
re-
gion
.The
sele
cted
chim
eric
viru
ses
wer
ene
utra
lized
byan
ti-V
3lo
opM
Abs
.
The
chim
eric
viru
ses
elic
ited
pote
ntN
Abs
agai
nstA
LA-1
and
MN
ingu
inea
pigs
.
[Sor
ense
n(1
994)
]A
.S
oren
sen,
C.
Nie
lsen
,M
.A
rend
rup,
H.
Cla
usen
,J.
Nie
lsen
,E.O
sina
ga,A
.Ros
eto,
&J.
-E.S
.Han
sen.
Neu
tral
izat
ion
epito
pes
onH
IVps
eudo
type
dw
ithH
TLV
-I:C
onse
rvat
ion
ofca
rboh
ydra
teep
itope
s.J
Acq
Imm
un
eD
ef
Syn
d7:11
6–12
3,19
94.
(Med
line:
9413
3079
)N
otes
:P
seud
otyp
esw
ere
form
edw
ithH
IVan
dH
TLV
-I.M
Ab
9284
,dire
cted
atth
eV
3lo
opof
gp12
0,fa
iled
toin
hibi
tthe
infe
ctio
nof
CD
-4ne
gativ
ece
llsw
ithps
eudo
type
s,bu
tan
ti-H
TLV
seru
mdi
din
hibi
tin
fect
ion.
HIV
and
HT
LV-I
appe
arto
indu
ceco
mm
onca
rboh
ydra
tene
utra
lizin
gep
itope
s.
[Spe
ar(1
994)
]G
.T.
Spe
ar,
D.
M.
Take
fman
,S
.S
harp
e,M
.G
hass
emi,
&S
.Z
olla
-Paz
ner.
Ant
ibod
ies
toth
eH
IV-1
V3
loop
inse
rum
from
infe
cted
pers
ons
cont
ribut
ea
maj
orpr
opor
tion
ofim
mun
eef
fect
orfu
nctio
nsin
clud
-in
gco
mpl
emen
tac
tivat
ion,
antib
ody
bind
ing,
and
neut
raliz
atio
n.V
irolo
gy
204:
609–
15,1
994.
(Med
line:
9502
7690
).
[Spe
ar(1
993)
]G
.T.
Spe
ar,
D.
M.
Take
fman
,B
.L.
Sul
livan
,A
.L.
Land
ay,
&S
.Zol
la-P
azne
r.C
ompl
emen
tact
ivat
ion
byhu
man
mon
oclo
nala
ntib
od-
ies
tohu
man
imm
unod
efici
ency
viru
s.JV
irol6
7:53
–59,
1993
.(M
edlin
e:93
1008
37)
Not
es:
Thi
sst
udy
look
edat
the
abili
tyof
16hu
man
MA
bsto
activ
ate
com
plem
ent.
MA
bsdi
rect
edag
ains
tth
eV
3re
gion
coul
din
duce
C3
depo
sitio
non
infe
cted
cells
and
viro
lysi
sof
free
viru
s,bu
tan
tibod
-ie
sto
the
CD
4BS
and
C-t
erm
inal
regi
onan
dtw
ore
gion
sin
gp41
coul
din
duce
noco
mpl
emen
tmed
iate
def
fect
s.P
re-t
reat
men
twith
sCD
4co
uld
in-
crea
seco
mpl
emen
t-m
edia
ted
effe
cts
ofan
ti-gp
41M
Abs
,but
decr
ease
dth
eco
mpl
emen
t-m
edia
ted
effe
cts
ofV
3M
Abs
.A
nti-g
p41
MA
bsw
ere
able
toaf
fect
IIIB
butn
otM
Nvi
roly
sis,
sugg
estin
gsp
onta
neou
ssh
eddi
ngof
gp12
0on
IIIB
virio
nsex
pose
sgp
41ep
itope
s.Ig
Gis
otyp
edi
dno
tap
pear
toha
vean
effe
cton
viro
lysi
sor
C3
depo
sitio
n.
[Spe
rlagh
(199
3)]
M.
Spe
rlagh
,K
.S
tefa
no,
F.G
onza
lez-
Sca
rano
,S
.Li
ang,
J.H
oxie
,H.M
aruy
ama,
M.P
rew
ett,
S.M
atsu
shito
,&D
.Her
lyn.
Mon
oclo
nal
anti-
idio
type
antib
odie
sth
atm
imic
the
epito
peon
gp12
0de
fined
byth
ean
ti-H
IV-1
mon
oclo
nal
antib
ody
0.5β.
AID
S7:
1553
–155
9,19
93.
(Med
line:
9411
4127
).
[Sta
mat
atos
&C
heng
-May
er(1
995)
]L.
Sta
mat
atos
&C
.Che
ng-M
ayer
.Str
uc-
tura
lmod
ulat
ions
ofth
een
velo
pegp
120
glyc
opro
tein
ofhu
man
imm
unod
-efi
cien
cyvi
rus
type
1up
onol
igom
eriz
atio
nan
dth
edi
ffere
ntia
lV
3lo
op
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-41
DE
C20
00
epito
peex
posu
reof
isol
ates
disp
layi
ngdi
stin
cttr
opis
mup
onvi
ral-s
olub
lere
cept
orbi
ndin
g.J
Viro
l69:
6191
–619
8,19
95.
(Med
line:
9539
5953
).
[Sta
mat
atos
&C
heng
-May
er(1
998)
]L.
Sta
mat
atos
&C
.C
heng
-May
er.
An
enve
lope
mod
ifica
tion
that
rend
ers
apr
imar
y,ne
utra
lizat
ion-
resi
stan
tcla
deB
hum
anim
mun
odefi
cien
cyvi
rus
type
1is
olat
ehi
ghly
susc
eptib
leto
neu-
tral
izat
ion
byse
rafr
omot
her
clad
es.JV
irol7
2:78
40–5
,19
98.
(Med
line:
9840
6184
).
[Sta
mat
atos
(199
7)]
L.S
tam
atat
os,S
.Zol
la-P
azne
r,M
.K.G
orny
,&C
.Che
ng-
May
er.
Bin
ding
ofan
tibod
ies
tovi
rion-
asso
ciat
edgp
120
mol
ecul
esof
prim
ary-
like
hum
anim
mun
odefi
cien
cyvi
rus
type
1(H
IV-1
)is
olat
es:
ef-
fect
onH
IV-1
infe
ctio
nof
mac
roph
ages
and
perip
hera
lblo
odm
onon
ucle
arce
lls.V
irolo
gy
229:
360–
9,19
97.
(Med
line:
9727
1298
).
[Sta
nfiel
d(1
999)
]R
.Sta
nfiel
d,E
.Cab
ezas
,A.S
atte
rthw
ait,
E.S
tura
,A.P
rofy
,&
I.W
ilson
.D
ual
conf
orm
atio
nsfo
rth
eH
IV-1
gp12
0V
3lo
opin
com
-pl
exes
with
diffe
rent
neut
raliz
ing
Fab
s.Str
uct
ure
7:13
1–42
,199
9.(M
edlin
e:99
1481
21).
[Stig
ler
(199
5)]
R.
D.
Stig
ler,
F.R
uker
,D
.K
atin
ger,
G.
Elli
ott,
W.
Hoh
ne,
P.H
enkl
ein,
J.X
.Ho,
K.K
eelin
g,D
.C.C
arte
r,E
.Nug
el,&
etal
.In
tera
ctio
nbe
twee
na
Fab
frag
men
tag
ains
tgp
41of
hum
anim
mun
odefi
cien
cyvi
rus
1an
dits
pept
ide
epito
pe:c
hara
cter
izat
ion
usin
ga
pept
ide
epito
pelib
rary
and
mol
ecul
arm
odel
ing.P
rote
inE
ng8
:471
–9,1
995.
(Med
line:
9601
6641
).
[Sto
iber
(199
6)]
H.
Sto
iber
,C
.P
inte
r,A
.G
.S
icca
rdi,
A.
Cliv
io,
&M
.P.
Die
rich.
Effi
cien
tde
stru
ctio
nof
hum
anim
mun
odefi
cien
cyvi
rus
inhu
man
seru
mby
inhi
bitin
gth
epr
otec
tive
actio
nof
com
plem
entf
acto
rH
and
deca
yac
cele
ratin
gfa
ctor
(DA
F,C
D55
).JE
xpM
ed1
83:3
07–3
10,1
996.
(Med
line:
9613
6775
)N
otes
:H
IVan
dH
IV-in
fect
edce
llsar
eno
tsu
bjec
tto
effic
ient
com
plem
ent-
med
iate
dly
sis,
even
inth
epr
esen
ceof
HIV
-spe
cific
antib
od-
ies.
HIV
isin
trin
sica
llyre
sist
antt
ohu
man
com
plem
ent.
Dec
ayac
cele
ratin
gfa
ctor
(DA
F)
and
hum
anco
mpl
emen
tfa
ctor
H(C
FH
),a
hum
oral
nega
tive
regu
lato
rof
com
plem
entw
hich
bind
sto
gp41
are
criti
calf
orth
isre
sist
ance
.M
Ab
2F5
can
inhi
bitC
HF
bind
ing
and
faci
litat
eco
mpl
emen
tmed
iate
dly
sis.
[Sug
iura
(199
9)]
W.S
ugiu
ra,C
.C.B
rode
r,B
.Mos
s,&
P.L.
Ear
l.C
hara
cter
i-za
tion
ofco
nfor
mat
ion-
depe
nden
tant
i-gp1
20m
urin
em
onoc
lona
lant
ibod
ies
prod
uced
byim
mun
izat
ion
with
mon
omer
ican
dol
igom
eric
hum
anim
mun
-od
efici
ency
viru
sty
pe1
enve
lope
prot
eins
.Viro
log
y25
4:25
7–67
,19
99.
(Med
line:
9914
3340
).
[Sul
livan
(199
8a)]
N.S
ulliv
an,Y
.Sun
,J.B
inle
y,J.
Lee,
C.3
rd.B
arba
s,P.
W.
Par
ren,
D.
R.
Bur
ton,
&J.
Sod
rosk
i.D
eter
min
ants
ofhu
man
imm
unod
e-fic
ienc
yvi
rus
type
1en
velo
pegl
ycop
rote
inac
tivat
ion
byso
lubl
eC
D4
and
mon
oclo
nala
ntib
odie
s.JV
irol7
2:63
32–8
,199
8a.
(Med
line:
9832
5144
).
[Sul
livan
(199
5)]
N.
Sul
livan
,Y.
Sun
,J.
Li,
W.
Hof
man
n,&
J.S
odro
ski.
Rep
licat
ive
func
tion
and
neut
raliz
atio
nse
nsiti
vity
ofen
velo
pegl
ycop
rote
ins
from
prim
ary
and
T-ce
lllin
e-pa
ssag
edhu
man
imm
unod
efici
ency
viru
sty
pe1
isol
ates
.JV
irol6
9:44
13–4
422,
1995
.(M
edlin
e:95
2874
98)
Not
es:T
hree
gp12
0m
olec
ules
deriv
edfr
ompr
imar
yis
olat
esw
ere
com
pare
dto
T-ce
llad
apte
dlin
esH
XB
c2an
dM
N.C
ompl
emen
tatio
nex
perim
ents
show
edvi
ral
entr
yin
tope
riphe
ralb
lood
mon
onuc
lear
cell
targ
ets
was
five-
fold
less
effi-
cien
tfo
rpr
imar
yis
olat
es.
Ant
i-CD
4bi
ndin
gsi
tene
utra
lizin
gM
Abs
wer
efa
rle
sspo
tent
agai
nst
prim
ary
isol
ates
,an
dth
esi
ngle
anti-
V3
MA
bte
sted
was
3-fo
ldle
sspo
tent
.The
diffe
renc
esin
neut
raliz
atio
nef
ficie
ncy
coul
dno
tbe
attr
ibut
edto
diffe
renc
esin
affin
ityfo
rmon
omer
icgp
120,
butw
ere
rela
ted
tobi
ndin
gto
the
olig
omer
icco
mpl
ex.E
nhan
ced
infe
ctiv
ityof
prim
ary
iso-
late
sw
asob
serv
edus
ing
sCD
4an
dM
Ab
F10
5,w
hich
can
neut
raliz
eT-
cell
adap
ted
stra
ins.
[Sul
livan
(199
8b)]
N.
Sul
livan
,Y.
Sun
,Q
.S
atte
ntau
,M
.T
hali,
D.
Wu,
G.
Den
isov
a,J.
Ger
shon
i,J.
Rob
inso
n,J.
Moo
re,
&J.
Sod
rosk
i.C
D4-
Indu
ced
conf
orm
atio
nalc
hang
esin
the
hum
anim
mun
odefi
cien
cyvi
rus
type
1gp
120
glyc
opro
tein
:con
sequ
ence
sfo
rviru
sen
try
and
neut
raliz
atio
n.J
Vi-
rol7
2:46
94–7
03,1
998b
.(M
edlin
e:98
2417
04)
Not
es:A
stud
yof
the
sCD
4in
duci
ble
MA
b17
bi,a
ndth
eM
Ab
CG
10th
atre
cogn
izes
agp
120-
CD
4co
m-
plex
.The
seep
itope
sar
em
inim
ally
acce
ssib
leup
onat
tach
men
tofg
p120
toth
ece
ll.T
heC
D4-
bind
ing
indu
ced
chan
ges
ingp
120
wer
est
udie
d,ex
plor
-in
gth
ese
ques
terin
gof
chem
okin
ere
cept
orbi
ndin
gsi
tes
from
the
hum
oral
resp
onse
.
[Sul
livan
(199
3)]
N.
Sul
livan
,M
.T
hali,
C.
Fur
man
,D
.H
o,&
J.S
odro
ski.
Effe
ctof
amin
oac
idch
ange
sin
the
V2
regi
onof
the
hum
anim
mun
odefi
-ci
ency
viru
sty
pe1
gp12
0gl
ycop
rote
inon
subu
nit
asso
ciat
ion,
sync
ytiu
mfo
rmat
ion,
and
reco
gniti
onby
ane
utra
lizin
gan
tibod
y.J
Viro
l67:
3674
–367
9,19
93.
(Med
line:
9326
7832
)N
otes
:Rec
ogni
tion
ofne
utra
lizin
gM
Ab
G3-
4w
asal
tere
dby
subs
titut
ions
in17
6to
184
inth
eV
2lo
op.
Som
ech
ange
sin
the
V2
loop
can
affe
ctsu
buni
tass
embl
y;ot
her
chan
ges
allo
wex
pres
sion
and
CD
4bi
ndin
gbu
tinh
ibit
sync
ytiu
mfo
rmat
ion
and
vira
lent
ry,s
ugge
stin
gth
atV
1/V
2m
aybe
invo
lved
inpo
stre
cept
orbi
ndin
gev
ents
.
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-42
DE
C20
00
[Sun
(198
9)]
N.
C.
Sun
,D
.D
.H
o,C
.R
.Y.
Sun
,R
.-S
.Li
ou,
W.
Gor
don,
M.S
.C.F
ung,
X.L
.Li,
R.C
.Tin
g,T.
-H.L
ee,N
.T.C
hang
,&T.
W.C
hang
.G
ener
atio
nan
dch
arac
teriz
atio
nof
mon
oclo
nal
antib
odie
sto
the
puta
tive
CD
4-bi
ndin
gdo
mai
nof
hum
anim
mun
odefi
cien
cyvi
rus
type
1gp
120.
JV
irol6
3:35
79–3
585,
1989
.(M
edlin
e:89
3425
91).
[Szi
lvay
(199
5)]
A.M
.Szi
lvay
,K.A
.Bro
ksta
d,R
.Kop
peru
d,G
.Hau
kene
s,&
K.H
.Kal
land
.N
ucle
arex
port
ofth
ehu
man
imm
unod
efici
ency
viru
sty
pe1
nucl
eocy
topl
asm
icsh
uttle
prot
ein
Rev
ism
edia
ted
byits
activ
atio
ndo
mai
nan
dis
bloc
ked
bytr
ansd
omin
ant
nega
tive
mut
ants
.J
Viro
l69:
3315
–332
3,19
95.
(Med
line:
9526
4419
).
[Szi
lvay
(199
2)]
A.M
.Szi
lvay
,S.N
orne
s,I.
R.H
auga
n,L.
Ols
en,V
.R.P
rasa
d,C
.End
rese
n,S
.P.G
off,
&D
.E.H
ella
nd.
Epi
tope
map
ping
ofH
IV-1
reve
rse
tran
scrip
tase
with
mon
oclo
nala
ntib
odie
sth
atin
hibi
tpol
ymer
ase
and
RN
ase
Hac
tiviti
es.J
AID
S5:
647–
657,
1992
.(M
edlin
e:92
3091
78)N
otes
:20
MA
bsar
ede
scrib
ed,o
nly
five
are
able
tobi
ndto
shor
tpep
tides
.The
sefiv
eM
Abs
are
inse
nsiti
veto
mut
atio
nsth
roug
hou
tthe
rest
ofR
T.
[Tak
eda
(199
2)]
A.
Take
da,
J.E
.R
obin
son,
D.
D.
Ho,
C.
Deb
ouck
,N
.L.
Hai
gwoo
d,&
F.A
.Enn
is.D
istin
ctio
nof
hum
anim
mun
odefi
cien
cyvi
rus
type
1ne
utra
lizat
ion
and
infe
ctio
nen
hanc
emen
tby
hum
anm
onoc
lona
lant
ibod
ies
togl
ycop
rote
in12
0.J
Clin
Inv
89:1
952–
1957
,199
2.(M
edlin
e:92
2913
14)
Not
es:
Com
plem
ent
rece
ptor
sfo
rIg
Gon
mon
ocyt
icce
llsca
nse
rve
asa
mea
nsfo
rM
Ab
med
iate
den
hanc
emen
tofH
IV-1
infe
ctio
n.M
Abs
N70
-1.5
and
N70
-2.3
abi
nddi
stin
ctdi
scon
tinuo
usep
itope
sin
gp12
0.N
70-1
.5is
apo
tent
neut
raliz
ing
MA
bw
ithno
enha
ncin
gac
tivity
,whi
leN
70-2
.3a
does
n‘t
neut
raliz
ean
dm
edia
tes
enha
ncem
ento
fHIV
-1in
fect
ion.
[Tak
efm
an(1
998)
]D
.M.T
akef
man
,B.L
.Sul
livan
,B.E
.Sha
,&G
.T.S
pear
.M
echa
nism
sof
resi
stan
ceof
HIV
-1pr
imar
yis
olat
esto
com
plem
ent-
med
i-at
edly
sis.
Viro
log
y24
6:37
0–8,
1998
.(M
edlin
e:98
3277
85).
[Tan
chou
(199
5)]
V.Ta
ncho
u,T.
Del
auna
y,M
.Bod
eus,
B.R
oque
s,J.
L.D
arlix
,&
R.B
enar
ous.
Con
form
atio
nalc
hang
esbe
twee
nhu
man
imm
unod
efici
ency
viru
sty
pe1
nucl
eoca
psid
prot
ein
NC
p7an
dits
prec
urso
rNC
p15
asde
tect
edby
anti-
NC
p7m
onoc
lona
lan
tibod
ies.J
Ge
nV
irol7
6:24
57–2
466,
1995
.(M
edlin
e:96
0308
55).
[Tan
chou
(199
4)]
V.Ta
ncho
u,T.
Del
auna
y,H
.de
Roc
quig
ny,M
.Bod
eus,
J.-L
.D
arlix
,B.R
oque
s,&
R.B
enar
ous.
Mon
oclo
nala
ntib
ody-
med
iate
din
hibi
-tio
nof
RN
Abi
ndin
gan
dan
neal
ing
activ
ities
ofH
IVty
pe1
nucl
eoca
psid
pro-
tein
.AID
SR
es
Hu
mR
etr
oviru
ses10:9
83–9
93,1
994.
(Med
line:
9511
0646
).
[Tan
i(19
94)]
Y.Ta
ni,E
.Don
oghu
e,S
.Sha
rpe,
E.B
oone
,H.C
.Lan
e,S
.Zol
la-
Paz
ner,
&D
.I.
Coh
en.
Enh
ance
din
vitr
ohu
man
imm
unod
efici
ency
viru
sty
pe1
repl
icat
ion
inB
cells
expr
essi
ngsu
rfac
ean
tibod
yto
the
TM
env
prot
ein.
JV
irol6
8:19
42–1
950,
1994
.(M
edlin
e:94
1498
89)N
otes
:The
MA
b98
-6w
asex
pres
sed
asa
surf
ace
anti-
gp41
mon
oclo
nala
ntib
ody
rece
ptor
for
gp41
(sIg
/gp4
1)by
tran
sfec
tion
into
aC
D4-
nega
tive
B-c
elll
ine.
Tra
nsfe
cted
cells
coul
dbi
ndH
IVen
velo
pe,
but
coul
dno
tbe
infe
cted
byH
IV-1
.W
hen
CD
4de
liver
edby
retr
ovira
lco
nstr
ucts
was
expr
esse
don
thes
ece
lls,
they
acqu
ired
the
abili
tyto
repl
icat
eH
IV-1
,an
dsI
g/gp
41sp
ecifi
cally
enha
nced
vira
lrep
licat
ion.
[Tat
sum
i(19
90)]
M.
Tats
umi,
C.
Dev
aux,
F.K
ouril
sky,
&J.
C.
Che
rman
n.C
hara
cter
izat
ion
ofm
onoc
lona
lan
tibod
ies
dire
cted
agai
nst
dist
inct
con-
serv
edep
itope
sof
hum
anim
mun
odefi
cien
cyvi
rus
type
1co
repr
otei
ns.
Mo
lCe
llB
ioch
em
96:1
27–1
36,1
990.
(Med
line:
9110
9746
).
[Tee
uwse
n(1
990)
]V.
J.Te
euw
sen,
K.
H.
Sie
belin
k,S
.C
rush
-Sta
nton
,B
.S
wer
dlow
,J.
J.S
chal
ken,
J.G
ouds
mit,
R.
van
deA
kker
,M
.J.
Stu
kart
,F.
G.
Uyt
deha
ag,
&A
.D
.O
ster
haus
.P
rodu
ctio
nan
dch
arac
teriz
atio
nof
ahu
man
mon
oclo
nala
ntib
ody,
reac
tive
with
aco
nser
ved
epito
peon
gp41
ofhu
man
imm
unod
efici
ency
viru
sty
peI.AID
SR
es
Hu
mR
etr
oviru
ses6:38
1–39
2,19
90.
(Med
line:
9025
3925
).
[Tew
ari(
1998
)]D
.Tew
ari,
S.L
.Gol
dste
in,A
.L.N
otki
ns,&
P.Z
hou.
cDN
Aen
codi
nga
sing
le-c
hain
antib
ody
toH
IVp1
7w
ithcy
topl
asm
icor
nucl
ear
rete
ntio
nsi
gnal
sin
hibi
tsH
IV-1
repl
icat
ion.J
Imm
un
ol1
61:2
642–
7,19
98.
(Med
line:
9839
1083
).
[Tha
li(1
994)
]M
.T
hali,
M.
Cha
rles,
C.
Fur
man
,L.
Cav
acin
i,M
.P
osne
r,J.
Rob
inso
n,&
J.S
odro
ski.
Res
ista
nce
tone
utra
lizat
ion
bybr
oadl
yre
activ
ean
tibod
ies
toth
ehu
man
imm
unod
efici
ency
viru
sty
pe1
gp12
0gl
ycop
rote
inco
nfer
red
bya
gp41
amin
oac
idch
ange
.J
Viro
l68:
674–
680,
1994
.(M
edlin
e:94
1184
14)
Not
es:A
T→A
amin
oac
idsu
bstit
utio
nat
posi
tion
582
ofgp
41co
nfer
red
resi
stan
ceto
neut
raliz
atio
nto
30%
ofH
IVpo
sitiv
ese
ra(W
ilson
eta
l.J
Viro
l64:
3240
-48
(199
0)).
Mon
oclo
nala
ntib
odie
sth
atbo
und
toth
eC
D4
bind
ing
site
wer
eun
able
tone
utra
lize
this
viru
s,bu
tthe
mut
atio
ndi
dno
tre
duce
the
neut
raliz
ing
capa
city
ofa
V2
regi
onM
Ab
G3-
4,V
3re
gion
MA
bs,o
rgp
41ne
utra
lizin
gM
Ab
2F5.
[Tha
li(1
992a
)]M
.Tha
li,C
.Fur
man
,D.D
.Ho,
J.R
obin
son,
S.T
illey
,A.P
inte
r,&
J.S
odro
ski.
Dis
cont
inuo
us,c
onse
rved
neut
raliz
atio
nep
itope
sov
erla
ppin
g
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-43
DE
C20
00
the
CD
4-bi
ndin
gre
gion
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
gp12
0en
-ve
lope
glyc
opro
tein
.JV
irol6
6:56
35–5
641,
1992
a.(M
edlin
e:92
3651
62)
Not
es:
Map
sth
ere
latio
nshi
pbe
twee
nam
ino
acid
subs
titut
ions
that
redu
ceC
D4-
gp12
0in
tera
ctio
n,an
dam
ino
acid
subs
titut
ions
that
redu
ceth
ebi
ndin
gof
disc
ontin
uous
epito
peM
Abs
that
inhi
bitC
D4
bind
ing.
[Tha
li(1
992b
)]M
.Tha
li,C
.Fur
man
,B.W
ahre
n,M
.Pos
ner,
D.H
o,J.
Rob
in-
son,
&J.
Sod
rosk
i.C
oope
rativ
ityof
neut
raliz
ing
antib
odie
sdi
rect
edag
ains
tth
eV
3an
dC
D4
bind
ing
regi
ons
ofth
eH
IV-1
gp12
0en
velo
pegl
ycop
rote
in.
JA
cqIm
mu
ne
De
fSyn
d5:59
1–59
9,19
92b.
(Med
line:
9226
9113
).
[Tha
li(1
993)
]M
.T
hali,
J.P.
Moo
re,
C.
Fur
man
,M
.C
harle
s,D
.D
.H
o,J.
Rob
inso
n,&
J.S
odro
ski.
Cha
ract
eriz
atio
nof
cons
erve
dhu
man
imm
un-
odefi
cien
cyvi
rus
type
1gp
120
neut
raliz
atio
nep
itope
sex
pose
dup
ongp
120-
CD
4bi
ndin
g.J
Viro
l67:
3978
–398
8,19
93.(
Med
line:
9328
7215
)Not
es:F
ive
regi
ons
are
likel
yto
cont
ribut
eto
the
48d
and
17b
disc
ontin
uous
epito
pes,
eith
erdi
rect
lyor
thro
ugh
loca
lcon
form
atio
nale
ffect
s:th
ehy
drop
hobi
crin
g-lik
est
ruct
ure
form
edby
the
disu
lfide
bond
that
links
C3
and
C4,
the
base
ofth
est
em-lo
opth
atco
ntai
nsV
1an
dV
2,an
dth
ehy
drop
hobi
cre
gion
inC
2fr
omA
rg25
2to
Asp
262.
Add
ition
ally
chan
ges
inG
lu37
0,an
dM
et47
5in
C5,
affe
cted
bind
ing
and
neut
raliz
atio
n.T
hehy
drop
hobi
cch
arac
ter
ofth
ese
criti
calr
egio
nsis
cons
iste
ntw
ithth
elim
ited
expo
sure
ongp
120
prio
rto
CD
4bi
ndin
g.
[Tha
li(1
991)
]M
.Tha
li,U
.Ols
hevs
ky,C
.Fur
man
,D.G
abuz
da,M
.Pos
ner,
&J.
Sod
rosk
i.C
hara
cter
izat
ion
ofa
disc
ontin
uous
hum
anim
mun
odefi
cien
cyvi
rus
type
1gp
120
epito
pere
cogn
ized
bya
broa
dly
reac
tive
neut
raliz
ing
hum
anm
onoc
lona
lant
ibod
y.JV
irol6
5(11
):618
8–61
93,
1991
.(M
edlin
e:92
0155
17)
Not
es:
An
early
deta
iled
char
acte
rizat
ion
ofth
em
utat
ions
that
inhi
bitt
hene
utra
lizat
ion
capa
city
ofth
eM
Ab
F10
5,th
atbi
nds
toa
disc
on-
tinuo
usep
itope
and
inhi
bits
CD
4bi
ndin
gto
gp12
0.
[Thi
riart
(198
9)]
C.
Thi
riart
,M
.F
ranc
otte
,J.
Coh
en,
C.
Col
ligno
n,A
.D
el-
ers,
S.
Kum
mer
t,C
.M
olito
r,D
.G
illes
,P.
Roe
lant
s,F.
Van
Wijn
enda
ele,
M.
De
Wild
e,&
C.
Bru
ck.
Sev
eral
antig
enic
dete
rmin
ants
expo
sed
onth
egp
120
moi
ety
ofH
IV-1
gp16
0ar
ehi
dden
onth
em
atur
egp
120.
JIm
mu
no
l14
3:18
32–1
836,
1989
.(M
edlin
e:89
3813
16).
[Till
(198
9)]
M.
A.
Till
,S
.Z
olla
-Paz
ner,
M.
K.
Gor
ny,
J.W
.U
hr,
&E
.S
.V
itetta
.H
uman
imm
unod
efici
ency
viru
s-in
fect
edT
cells
and
mon
ocyt
esar
eki
lled
bym
onoc
lona
lhum
anan
ti-gp
41an
tibod
ies
coup
led
toric
inA
chai
n.P
roc
Na
tlA
cad
Sci
US
A86:
1987
–199
1,19
89.
(Med
line:
8918
4552
).
[Till
ey(1
992)
]S
.A.T
illey
,W.J
.Hon
nen,
M.E
.Rac
ho,T
.-C
.Cho
u,&
A.P
in-
ter.
Syn
ergi
stic
neut
raliz
atio
nof
HIV
-1by
hum
anm
onoc
lona
lant
ibod
ies
agai
nst
the
V3
loop
and
the
CD
4-bi
ndin
gsi
teof
gp12
0.AID
SR
es
Hu
mR
etr
oviru
ses8
:461
–467
,199
2.(M
edlin
e:92
2876
31).
[Till
ey(1
991a
)]S
.A
.T
illey
,W
.J.
Hon
nen,
M.
E.
Rac
ho,
M.
Hilg
artn
er,
&A
.P
inte
r.A
hum
anm
onoc
lona
lan
tibod
yag
ains
tth
eC
D4-
bind
ing
site
ofH
IV-1
gp12
0ex
hibi
tspo
tent
,br
oadl
yne
utra
lizin
gac
tivity
.Re
sV
irol
142:
247–
259,
1991
a.(M
edlin
e:92
1795
21)
Not
es:
Cha
ract
eriz
atio
nof
hu-
man
neut
raliz
ing
MA
b11
25H
.
[Till
ey(1
991b
)]S
.A
.T
illey
,W
.J.
Hon
nen,
M.
E.
Rac
ho,
M.
Hilg
artn
er,
&A
.Pin
ter.
Hum
anM
onoc
lona
lAnt
ibod
ies
Aga
inst
the
Put
ativ
eC
D4
Bin
ding
Site
and
the
V3
Loop
ofH
IVgp
120
Act
inC
once
rtto
Neu
tral
ize
Viru
s.V
IIIn
tern
atio
na
lCo
nfe
ren
ceo
nA
IDS19
91:p
.39,
1991
b.N
otes
:Aid
slin
e:10
0709
1A
bstr
act7
0.
[Tis
dale
(198
8)]
M.T
isda
le,P
.Ert
l,B
.A.L
arde
r,D
.J.M
.Pur
ifoy,
G.D
arby
,&
K.L
.Pow
ell.
Cha
ract
eriz
atio
nof
hum
anim
mun
odefi
cien
cyvi
rus
type
1re
vers
etr
ansc
ripta
seby
usin
gm
onoc
lona
lant
ibod
ies:
role
ofth
eC
term
inus
inan
tibod
yre
activ
ityan
den
zym
efu
nctio
n.JV
irol6
2:36
62–3
667,
1988
.(M
edlin
e:88
3331
39).
[Too
hey
(199
5)]
K.
Tooh
ey,
K.
Weh
rly,
J.N
ishi
o,S
.P
erry
man
,&
B.
Che
se-
bro.
Hum
anim
mun
odefi
cien
cyvi
rus
enve
lope
V1
and
V2
regi
ons
influ
ence
repl
icat
ion
effic
ienc
yin
mac
roph
ages
byaf
fect
ing
viru
ssp
read
.V
irolo
gy
213:
70–9
,199
5.(M
edlin
e:96
0364
81).
[Tor
nato
re(1
994)
]C
.Tor
nato
re,K
.Mey
ers,
W.A
twoo
d,K
.Con
ant,
&E
.Ma-
jor.
Tem
pora
lpat
tern
sof
hum
anim
mun
odefi
cien
cyvi
rus
type
1tr
ansc
ripts
inhu
man
feta
last
rocy
tes.J
Viro
l68:
93–1
02,1
994.
(Med
line:
9407
6466
).
[Trk
ola
(199
6a)]
A.
Trk
ola,
T.D
ragi
c,J.
Art
hos,
J.M
.B
inle
y,W
.C
.O
lson
,G
.P.A
llaw
ay,C
.Che
ng-M
ayer
,J.R
obin
son,
P.J.
Mad
don,
&J.
P.M
oore
.C
D4-
depe
nden
t,an
tibod
y-se
nsiti
vein
tera
ctio
nsbe
twee
nH
IV-1
and
itsco
-re
cept
orC
CR
-5.N
atu
re38
4:18
4–18
7,19
96a.
(Med
line:
9706
4177
)N
otes
:C
CR
-5is
aco
-fac
tor
for
fusi
onof
HIV
-1st
rain
sof
the
non-
sync
ytiu
m-
indu
cing
(NS
I)ph
enot
ype
with
CD
4+T-
cells
.CD
4bi
ndin
ggr
eatly
incr
ease
sth
eef
ficie
ncy
ofgp
120-
CC
R-5
inte
ract
ion.
Neu
tral
izin
gM
Abs
agai
nst
the
V3
loop
and
CD
4-in
duce
dep
itope
son
gp12
0in
hibi
ted
the
inte
ract
ion
ofgp
120
with
CC
R-5
,with
outa
ffect
ing
gp12
0-C
D4
bind
ing.
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-44
DE
C20
00
[Trk
ola
(199
8)]
A.T
rkol
a,T.
Ket
as,V
.N.K
ewal
ram
ani,
F.E
ndor
f,J.
M.B
in-
ley,
H.K
atin
ger,
J.R
obin
son,
D.R
.Litt
man
,&J.
P.M
oore
.N
eutr
aliz
atio
nse
nsiti
vity
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
prim
ary
isol
ates
toan
-tib
odie
san
dC
D4-
base
dre
agen
tsis
inde
pend
ento
fcor
ecep
toru
sage
.J
Viro
l72
:187
6–85
,199
8.(M
edlin
e:98
1390
79).
[Trk
ola
(199
5)]
A.T
rkol
a,A
.B.P
omal
es,H
.Yua
n,B
.Kor
ber,
P.J.
Mad
don,
G.P
.Alla
way
,H.K
atin
ger,
C.F
.Bar
bas
III,D
.R.B
urto
n,D
.D.H
o,&
J.P.
Moo
re.
Cro
ss-c
lade
neut
raliz
atio
nof
prim
ary
isol
ates
ofhu
man
imm
un-
odefi
cien
cyvi
rus
type
1by
hum
anm
onoc
lona
lan
tibod
ies
and
tetr
amer
icC
D4-
IgG
.JV
irol6
9:66
09–6
617,
1995
.(M
edlin
e:96
0137
52)
Not
es:T
hree
MA
bs,I
gG1b
12,2
G12
,and
2F5
tetr
amer
icC
D4-
IgG
2w
ere
test
edfo
rth
eir
abili
tyto
neut
raliz
epr
imar
yis
olat
esfr
omcl
ades
A-F
.2F
5an
dC
D4-
IgG
2w
ere
able
tone
utra
lize
with
inan
dou
tsid
ecl
ade
Bw
itha
high
pote
ncy.
IgG
1b12
and
2G12
coul
dpo
tent
lyne
utra
lize
isol
ates
from
with
incl
ade
B,
buts
how
eda
redu
ctio
nin
effic
acy
outs
ide
ofcl
ade
B.2
F5
neut
raliz
atio
nw
asde
pend
ento
nth
epr
esen
ceof
the
sequ
ence
:LD
KW
.
[Trk
ola
(199
6b)]
A.T
rkol
a,M
.Pur
tsch
er,T
.Mus
ter,
C.B
alla
un,A
.Buc
hach
er,
N.S
ulliv
an,K
.Srin
ivas
an,J
.Sod
rosk
i,J.
P.M
oore
,&H
.Kat
inge
r.H
uman
mon
oclo
nal
antib
ody
2G12
defin
esa
dist
inct
ive
neut
raliz
atio
nep
itope
onth
egp
120
glyc
opro
tein
ofhu
man
imm
unod
efici
ency
viru
sty
pe1.
JV
irol
70:1
100–
1108
,199
6b.
(Med
line:
9613
5224
).
[Tru
jillo
(199
3)]
J.R
.Tru
jillo
,M.F
.McL
ane,
T.-H
.Lee
,&M
.Ess
ex.
Mol
ec-
ular
mim
icry
betw
een
the
hum
anim
mun
odefi
cien
cyvi
rus
type
1gp
120
V3
loop
and
hum
anbr
ain
prot
eins
.JV
irol
67:7
711–
7715
,19
93.
(Med
line:
9404
7398
).
[Tug
arin
ov(2
000)
]V.
Tug
arin
ov,
A.
Zvi
,R
.Le
vy,
Y.H
ayek
,S
.M
atsu
shita
,&
J.A
nglis
ter.
NM
Rst
ruct
ure
ofan
anti-
gp12
0an
tibod
yco
mpl
exw
itha
V3
pept
ide
reve
als
asu
rfac
eim
port
ant
for
co-r
ecep
tor
bind
ing
[InP
roce
ssC
itatio
n].S
tru
ctu
reFo
ldD
es8
:385
–95,
2000
.(M
edlin
e:20
2643
05).
[Tur
bica
(199
5)]
I.T
urbi
ca,M
.Pos
ner,
C.B
ruck
,&F.
Bar
in.
Sim
ple
enzy
me
imm
unoa
ssay
for
titra
tion
ofan
tibod
ies
toth
eC
D4-
bind
ing
site
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
gp12
0.JC
linM
icro
bio
l33
:331
9–33
23,
1995
.(M
edlin
e:96
1561
53).
[Tur
bica
(199
7)]
I.T
urbi
ca,
F.S
imon
,J.
M.
Bes
nier
,B
.Le
Jeun
e,P.
Cho
utet
and
AG
oude
au,&
F.B
arin
.Te
mpo
rald
evel
opm
enta
ndpr
ogno
stic
valu
eof
antib
ody
resp
onse
toth
em
ajor
neut
raliz
ing
epito
pes
ofgp
120
durin
gH
IV-1
infe
ctio
n.J
Me
dV
irol5
2:30
9–31
5,19
97.
(Med
line:
9735
3800
).
[Tyl
er(1
990)
]D
.S
.Ty
ler,
S.
D.
Sta
nley
,S
.Z
olla
-Paz
ner,
M.
K.
Gor
ny,
P.P.
Sha
dduc
k,A
.J.
Lang
lois
,T.
J.M
atth
ews,
D.
P.B
olog
nesi
,T.
J.P
alke
r,&
K.
J.W
einh
old.
Iden
tifica
tion
ofsi
tes
with
ingp
41th
atse
rve
asta
rget
sfo
ran
tibod
y-de
pend
ent
cellu
lar
cyto
toxi
city
byus
ing
hum
anm
onoc
lona
lan
tibod
ies.
JIm
mu
no
l145
:327
6–32
82,1
990.
(Med
line:
9103
6969
).
[Uge
n(1
993)
]K
.E.U
gen,
Y.R
efal
eli,
U.Z
iegn
er,M
.Aga
djan
yan,
M.A
.R.
Sat
re,
V.S
rikan
tan,
B.
Wan
g,A
.S
ato,
W.
V.W
illia
ms,
&D
.B
.W
eine
r.G
ener
atio
nof
mon
oclo
nala
ntib
odie
sag
ains
tth
eam
ino
term
inus
ofgp
120
that
elic
itan
tibod
y-de
pend
entc
ellu
larc
ytot
oxic
ity.
Va
ccin
es
93p
ages
215–
221,
1993
.N
otes
:E
dito
rs:
F.B
row
n,H
.S
.G
insb
erg
and
R.
Lern
er,
Col
dS
prin
gH
arbo
rLa
bora
tory
Pre
ss,C
old
Spr
ing
Har
bor,
NY.
[Ugo
lini(
1997
)]S
.Ugo
lini,
I.M
ondo
r,P.
W.H
.IP
arre
n,D
.R.B
urto
n,S
.A.
Till
ey,P
.J.K
lass
e,&
Q.J
.Sat
tent
au.I
nhib
ition
ofvi
rus
atta
chm
entt
oC
D4+
targ
etce
llsis
am
ajor
mec
hani
smof
Tce
lllin
e-ad
apte
dH
IV-1
neut
raliz
atio
n.J
Exp
Me
d186
:128
7–12
98,1
997.
(Med
line:
9747
7412
).
[Val
enzu
ela
(199
8)]
A.
Vale
nzue
la,
J.B
lanc
o,B
.K
rust
,R
.F
ranc
o,&
A.
G.
Hov
anes
sian
.Neu
tral
izin
gA
ntib
odie
sag
ains
tthe
V3
loop
ofhu
man
imm
un-
odefi
cien
cyty
pe1
gp12
0bl
ock
the
CD
4-de
pend
enta
ndin
depe
nden
tbin
ding
ofth
evi
rus
toce
lls.J
Viro
l71:
8289
–829
8,19
98.
(Med
line:
9800
1346
).
[Val
vatn
e(1
996)
]H
.Val
vatn
e,A
.M.S
zilv
ay,&
D.E
.Hel
land
.A
mon
oclo
nal
antib
ody
defin
esa
nove
lHIV
type
1Ta
tdo
mai
nin
volv
edin
tran
s-ce
llula
rtr
ans-
activ
atio
n.A
IDS
Re
sH
um
Re
trov
iru
ses12:6
11–6
19,1
996.
(Med
line:
9629
1772
)N
otes
:CAT
and
beta
-gal
acto
sida
seas
says
,and
imm
unofl
uore
s-ce
nce
anal
ysis
wer
eus
edto
stud
yth
ece
llula
rupt
ake
ofth
eH
IV-1
Tatp
rote
in.
AM
Ab
bind
ing
toth
eba
sic
dom
ain
and
the
RG
Dse
quen
cein
hibi
tstr
ans-
activ
atio
nby
exog
enou
sTa
t.T
hein
hibi
tion
ofth
ece
llula
rupt
ake
ofTa
tby
anan
ti-Ta
tmon
oclo
nala
ntib
ody
and
byth
ese
rum
com
pone
nts
impl
ies
spec
ific
bind
ing
ofTa
tto
the
cell
mem
bran
e.
[Van
Cot
t(19
95)]
T.C
.Van
Cot
t,F.
R.B
ethk
e,D
.S.B
urke
,R.R
.Red
field
,&D
.L.B
irx.L
ack
ofin
duct
ion
ofan
tibod
ies
spec
ific
forc
onse
rved
,dis
cont
in-
uous
epito
pes
ofH
IV-1
enve
lope
glyc
opro
tein
byca
ndid
ate
AID
Sva
ccin
es.
JIm
mu
no
l155
:410
0–41
10,1
995.
(Med
line:
9600
3456
)N
otes
:The
Ab
re-
spon
sein
both
HIV
-1in
fect
edan
dun
infe
cted
volu
ntee
rsim
mun
ized
with
HIV
-1re
cen
velo
pesu
buni
tvac
cine
s(G
enen
tech
gp12
0IIIB
,Mic
roG
eneS
ysgp
160I
IIB,
orIm
mun
oAG
gp16
0IIIB
)pr
efer
entia
llyin
duce
dA
bsre
activ
eon
lyto
the
dena
ture
dfo
rmof
gp12
0.T
his
may
expl
ain
the
inab
ility
ofth
eva
ccin
eese
rato
neut
raliz
epr
imar
yH
IV-1
isol
ates
.
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-45
DE
C20
00
[Van
Cot
t(19
94)]
T.C
.Va
nCot
t,F.
R.
Bet
hke,
V.R
.P
olon
is,
M.
K.
Gor
ny,
S.Z
olla
-Paz
ner,
R.R
.Red
field
,&D
.L.B
irx.
Dis
soci
atio
nra
teof
antib
ody-
gp12
0bi
ndin
gin
tera
ctio
nsis
pred
ictiv
eof
V3-
med
iate
dne
utra
lizat
ion
ofH
IV-1
.J
Imm
un
ol1
53:4
49–4
59,1
994.
(Med
line:
9426
7254
)N
otes
:Usi
ngsu
rfac
epl
asm
onre
sona
nce
itw
asfo
und
that
the
rate
ofth
edi
ssoc
iatio
nof
the
MA
b-gp
120
com
plex
,bu
tno
tth
eas
soci
atio
nra
te,
corr
elat
edw
ithM
Abs
abili
tyto
neut
raliz
eho
mol
ogou
svi
rus
(mea
sure
dby
50%
inhi
bitio
nof
p24
prod
uctio
n).A
ssoc
iatio
nco
nsta
nts
wer
esi
mila
rfo
ral
lMA
bste
sted
,va
ryin
gle
ssth
an4-
fold
.Dis
soci
atio
nra
teco
nsta
nts
wer
equ
iteva
riabl
e,w
ith10
0-fo
lddi
ffere
nces
obse
rved
.
[Vel
la(1
993)
]C
.Ve
lla,
M.
Fer
guso
n,G
.D
unn,
R.
Mel
oen,
H.
Lang
edijk
,D
.Eva
ns,&
P.D
.Min
or.
Cha
ract
eriz
atio
nan
dpr
imar
yst
ruct
ure
ofa
hum
anim
mun
odefi
cien
cyvi
rus
type
1(H
IV-1
)ne
utra
lizat
ion
dom
ain
aspr
esen
ted
bya
polio
viru
sty
pe1/
HIV
-1ch
imer
a.JG
en
Viro
l7:1
5–21
,199
3.(M
edlin
e:94
1037
63)
Not
es:T
his
stud
yel
abor
ated
ona
seto
fant
ibod
ies
first
repo
rted
inE
vans
et
al.,
1989
.N
otal
lof
the
neut
raliz
atio
nre
sults
are
cong
ruen
tbe
twee
nth
est
udie
s.T
hean
tibod
ies
inth
isst
udy
wer
era
ised
toa
regi
onin
clud
ing
the
cyto
plas
mic
dom
ain
ofgp
41in
sert
edin
toa
polio
viru
sty
pe1/
HIV
-1ch
imer
a.
[von
Bru
nn(1
993)
]A
.vo
nB
runn
,M
.B
rand
,C
.R
eich
hube
r,C
.M
orys
-W
ortm
ann,
F.D
einh
ardt
,&
F.S
chod
el.
Prin
cipa
lne
utra
lizin
gdo
mai
nof
HIV
-1is
high
lyim
mun
ogen
icw
hen
expr
esse
don
the
surf
ace
ofhe
patit
isB
core
part
icle
s.Va
ccin
e11:
817–
24,1
993.
(Med
line:
9336
2473
).
[Wag
ner
(199
6)]
R.W
agne
r,L.
Dem
l,R
.Sch
irmbe
ck,M
.Nie
drig
,J.R
eim
ann,
&H
.Wol
f.C
onst
ruct
ion,
expr
essi
on,a
ndim
mun
ogen
icity
ofch
imer
icH
IV-
1vi
rus-
like
part
icle
s.V
irolo
gy
220:
128–
140,
1996
.(M
edlin
e:96
2406
35).
[Wag
ner
(199
8)]
R.
Wag
ner,
V.J.
Teeu
wse
n,L.
Dem
l,F.
Not
ka,
A.
G.
Haa
ksm
a,S
.S.J
hagj
hoor
sing
h,H
.Nip
huis
,H.W
olf,
&J.
L.H
eene
y.C
y-to
toxi
cT
cells
and
neut
raliz
ing
antib
odie
sin
duce
din
rhes
usm
onke
ysby
viru
s-lik
epa
rtic
leH
IVva
ccin
esin
the
abse
nce
ofpr
otec
tion
from
SH
IVin
fect
ion.
Viro
log
y24
5:65
–74,
1998
.(M
edlin
e:98
2770
73)
Not
es:
Sel
fas
sem
bled
non-
infe
ctio
usvi
rus.
[Wai
nber
g&
Gu(
1995
)]M
.A
.W
ainb
erg
&Z
.G
u.Ta
rget
ing
HIV
reve
rse
tran
scrip
tase
inno
velw
ays.N
atM
ed1
:628
–629
,199
5.(M
edlin
e:96
0715
18)
Not
es:C
omm
enta
ryon
Mac
ieje
wsk
ie
tal.,
1995
.
[War
rier
(199
5)]
S.V
.War
rier,
E.M
urph
y,I.
Yoko
yam
a,&
S.A
.Till
ey.
Cha
r-ac
teriz
atio
nof
the
Varia
ble
Reg
ions
ofa
Chi
mpa
nzee
Mon
oclo
nalA
ntib
ody
with
Pot
ent
Neu
tral
izin
gA
ctiv
ityA
gain
stH
IV-1
.Mo
lIm
mu
no
l32:
1081
–10
92,1
995.
(Med
line:
9612
8277
).
[War
rier
(199
4)]
S.V
.War
rier,
A.P
inte
r,W
.J.H
onne
n,M
.Gira
rd,E
.Muc
h-m
ore,
&S
.A.T
illey
.Ano
vel,
glyc
an-d
epen
dent
epito
pein
the
V2
dom
ain
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
gp12
0is
reco
gniz
edby
ahi
ghly
po-
tent
,neu
tral
izin
gch
impa
nzee
mon
oclo
nala
ntib
ody.
JV
irol6
8:46
36–4
642,
1994
.(M
edlin
e:94
2679
27).
[War
rier
(199
6)]
S.V
.War
rier,
A.P
inte
r,W
.J.H
onne
n,&
S.A
.Till
ey.
Syn
er-
gist
icN
eutr
aliz
atio
nof
Hum
anIm
mun
odefi
cien
cyV
irus
Type
1by
aC
him
-pa
nzee
Mon
oclo
nalA
ntib
ody
agai
nstt
heV
2D
omai
nof
gp12
0in
Com
bina
-tio
nw
ithM
onoc
lona
lAnt
ibod
ies
agai
nstt
heV
3Lo
opan
dth
eC
D4-
Bin
ding
Site
.JV
irol7
0:44
66–4
473,
1996
.(M
edlin
e:96
2567
57).
[Wat
kins
(199
6)]
B.
A.
Wat
kins
,A
.E
.D
avis
,S
.F
iore
ntin
i,F.
diM
arzo
Vero
nese
,&
M.
S.
Rei
tzJr
.E
vide
nce
for
dist
inct
cont
ribut
ions
ofhe
avy
and
light
chai
nsto
rest
rictio
nof
antib
ody
reco
gniti
onof
the
HIV
-1pr
inci
pal
neut
raliz
atio
nde
term
inan
t.JIm
mu
no
l156
:167
6–16
83,
1996
.(M
edlin
e:96
1646
01).
[Wat
kins
(199
3)]
B.A
.Wat
kins
,M.S
.Rei
tz,C
.A.W
ilson
,K.A
ldric
h,A
.E.
Dav
is,&
M.R
ober
t-G
urof
f.Im
mun
ees
cape
byhu
man
imm
unod
efici
ency
viru
sty
pe1
from
neut
raliz
ing
antib
odie
s:ev
iden
cefo
rm
ultip
lepa
thw
ays.
JV
irol6
7:74
93–7
500,
1993
.(M
edlin
e:94
0473
66)
Not
es:A
neut
raliz
atio
nre
sist
ance
poin
tm
utat
ion
(HX
B2
A28
1V)
was
stud
ied
usin
ga
varie
tyof
MA
bs,
and
itw
assh
own
that
this
subs
titut
ion
affe
cts
adi
ffere
ntep
itope
than
apr
evio
usly
char
acte
rized
neut
raliz
atio
nes
cape
mut
ant(
A58
2T)(
Rei
tz19
88,W
ilson
1990
).
[Weh
rly&
Che
sebr
o(19
97)]
K.
Weh
rly&
B.
Che
sebr
o.p2
4an
tigen
capt
ure
assa
yfo
rqu
antifi
catio
nof
hum
anim
mun
odefi
cien
cyvi
rus
usin
gre
adily
avai
labl
ein
expe
nsiv
ere
agen
ts.
Me
tho
ds:
Aco
mp
an
ion
toM
eth
od
sin
En
zy-
mo
log
y12:
288–
93,1
997.
(Med
line:
9740
1510
).
[Wei
nber
g(1
997)
]J.
Wei
nber
g,H
.X
.Li
ao,
J.V.
Torr
es,
T.J.
Mat
thew
s,J.
Rob
inso
n,&
B.F
.Hay
nes.
Iden
tifica
tion
ofa
synt
hetic
pept
ide
that
mim
-ic
san
HIV
glyc
opro
tein
120
enve
lope
conf
orm
atio
nald
eter
min
ante
xpos
edfo
llow
ing
ligat
ion
ofgl
ycop
rote
in12
0by
CD
4.AID
SR
es
Hu
mR
etr
oviru
ses
13:6
57–6
4,19
97.
(Med
line:
9731
1517
).
[Wei
ssen
horn
(199
6)]
W.W
eiss
enho
rn,S
.A.W
hart
on,L
.J.C
alde
r,P.
L.E
arl,
B.M
oss,
E.A
lipra
ndis
,J.J
.Ske
hel,
&D
.C.W
iley.
The
ecto
dom
ain
ofH
IV-
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-46
DE
C20
00
1E
nvsu
buni
tgp4
1fo
rms
aso
lubl
e,al
pha-
helic
al,r
od-li
keol
igom
erin
the
abse
nce
ofgp
120
and
the
N-t
erm
inal
fusi
onpe
ptid
e.E
MB
OJ1
5:15
07–1
4,19
96.
(Med
line:
9620
3067
).
[Whi
te-S
char
f(19
93)]
M.
E.
Whi
te-S
char
f,B
.J.
Pot
ts,
L.M
.S
mith
,K
.A
.S
okol
owsk
i,J.
R.
Rus
che,
&S
.S
ilver
.B
road
lyne
utra
lizin
gm
onoc
lona
lan
tibod
ies
toth
eV
3re
gion
ofH
IV-1
can
beel
icite
dby
pept
ide
imm
uniz
a-tio
n.V
irolo
gy
192:
197–
206,
1993
.(M
edlin
e:93
2971
06)N
otes
:Usi
nga
V3
loop
pept
ide
asim
mun
ogen
,apa
nelo
f50
anti-
V3
neut
raliz
ing
mon
oclo
nal
antib
odie
sw
ere
gene
rate
d.F
our
ofth
emw
ere
char
acte
rized
inde
tail
inth
ispa
per.
[Wis
new
ski(
1995
)]A
.Wis
new
ski,
L.C
avac
ini,
G.K
ings
bury
,D.S
adde
n,&
M.
Pos
ner.
Ant
i-HIV
hum
anm
onoc
lona
lan
tibod
yva
riabl
ere
gion
gene
usag
e.J
Ce
llB
ioch
em
supp
le21
B:22
9,19
95.
[Wis
new
ski(
1996
)]A
.Wis
new
ski,
L.C
avac
ini,
&M
.Pos
ner.
Hum
anan
tibod
yva
riabl
ere
gion
gene
usag
ein
HIV
-1in
fect
ion.JA
cqu
irIm
mu
ne
De
ficS
ynd
rH
um
Re
trov
irol1
1:31
–38,
1996
.(M
edlin
e:96
1300
44).
[Wol
fe(1
996)
]E
.J.
Wol
fe,
L.A
.C
avac
ini,
M.
H.
Sam
ore,
M.
R.
Pos
ner,
C.K
ozia
l,C
.Spi
no,C
.B.T
rapn
ell,
N.K
ette
r,S
.Ham
mer
,&J.
G.G
ambe
r-to
glio
.Pha
rmac
okin
etic
sof
F10
5,a
hum
anm
onoc
lona
lant
ibod
y,in
pers
ons
infe
cted
with
hum
anim
mun
odefi
cien
cyvi
rus
type
1.Clin
Ph
arm
aco
lTh
er
59:6
62–6
67,1
996.
(Med
line:
9629
0506
).
[Wu
(199
3)]
J.W
u,E
.A
man
doro
n,X
.Li
,M
.A
.W
ainb
erg,
&M
.A
.P
ar-
niak
.M
onoc
lona
lA
ntib
ody-
med
iate
dIn
hibi
tion
ofH
IV-1
Rev
erse
Tra
n-sc
ripta
seP
olym
eras
eA
ctiv
ity.JB
iolC
he
m26
8:99
80–9
985,
1993
.(M
ed-
line:
9325
2974
).
[Wu
(199
6)]
L.W
u,N
.P.
Ger
ard,
R.
Wya
tt,H
.C
hoe,
C.
Par
olin
,N
.R
uff-
ing,
A.
Bor
setti
,A
.A
.C
ardo
so,
E.
Des
jard
in,
W.
New
man
,C
.G
erar
d,&
J.S
odro
ski.
CD
4-in
duce
din
tera
ctio
nof
prim
ary
HIV
-1gp
120
glyc
opro
tein
sw
ithth
ech
emok
ine
rece
ptor
CC
R-5
.N
atu
re38
4:17
9–18
3,19
96.
(Med
line:
9706
4176
)N
otes
:R
esul
tssu
gges
tth
atH
IV-1
atta
chm
ent
toC
D4
crea
tes
ahi
gh-a
ffini
tybi
ndin
gsi
tefo
rC
CR
-5,
lead
ing
tom
embr
ane
fusi
onan
dvi
rus
entr
y.C
D4-
indu
ced
orV
3ne
utra
lizin
gM
Abs
bloc
kth
ein
tera
ctio
nof
gp12
0-C
D4
com
plex
esw
ithC
CR
-5.
[Wu
(199
5)]
Z.
Wu,
S.
C.
Kay
man
,W
.H
onne
n,K
.R
eves
z,H
.C
hen,
S.
V.W
arrie
r,S
.A.T
illey
,J.M
cKea
ting,
C.S
hotto
n,&
A.P
inte
r.C
hara
cter
izat
ion
ofne
utra
lizat
ion
epito
pes
inth
eV
2re
gion
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
gp12
0:ro
leof
glyc
osyl
atio
nin
the
corr
ectf
oldi
ngof
the
V1/
V2
dom
ain.
JV
irol69
:227
1–22
78,
1995
.(M
edlin
e:95
1910
00)
Not
es:
Mos
tep
itope
sba
sed
only
onnu
mbe
ring.
[Wya
tt(1
997)
]R
.Wya
tt,E
.Des
jard
in,U
.Ols
hevs
ky,C
.Nix
on,J
.Bin
ley,
V.O
l-sh
evsk
y,&
J.S
odro
ski.
Ana
lysi
sof
the
inte
ract
ion
ofth
ehu
man
imm
unod
e-fic
ienc
yvi
rus
type
1gp
120
Env
elop
egl
ycop
rote
inw
ithth
egp
41tr
ansm
em-
bran
egl
ycop
rote
in.J
Viro
l71:
9722
–31,
1997
.(M
edlin
e:98
0376
89)N
otes
:T
his
stud
ych
arac
teriz
edth
ebi
ndin
gof
gp12
0an
dgp
41by
com
parin
gA
bre
activ
ityto
solu
ble
gp12
0an
dto
aso
lubl
eco
mpl
exof
gp12
0an
dgp
41ca
lled
sgp1
40.T
heoc
clus
ion
ofgp
120
epito
pes
inth
esg
p140
com
plex
pro-
vide
sa
guid
eto
the
gp12
0do
mai
nsth
atin
tera
ctw
ithgp
41,l
ocal
izin
gth
emin
C1
and
C5
ofgp
120.
Mut
atio
nsth
atdi
srup
tthe
bind
ing
ofth
eoc
clud
edan
tibod
ies
dono
tin
fluen
ceN
Ab
bind
ing
orC
D4
bind
ing,
thus
ifth
egp
41bi
ndin
gdo
mai
nis
dele
ted,
the
imm
unol
ogic
ally
desi
rabl
efe
atur
esof
gp12
0fo
rva
ccin
ede
sign
are
still
inta
ct.
[Wya
tt(1
998)
]R
.Wya
tt,P.
D.K
won
g,E
.Des
jard
ins,
R.W
.Sw
eet,
J.R
obin
-so
n,W
.A
.H
endr
icks
on,
&J.
G.
Sod
rosk
i.T
hean
tigen
icst
ruct
ure
ofth
eH
IVgp
120
enve
lope
glyc
opro
tein
.Na
ture
393:
705–
711,
1998
.(M
edlin
e:98
3033
86)
Not
es:C
omm
enti
n:N
atur
e19
98Ju
n18
;393
(668
6):6
30-1
.The
spat
ialo
rgan
izat
ion
ofth
ene
utra
lizin
gep
itope
sof
gp12
0is
desc
ribed
,bas
edon
epito
pem
aps
inte
rpre
ted
inth
eco
ntex
toft
heX
-ray
crys
tals
truc
ture
ofa
tern
ary
com
plex
that
incl
udes
agp
120
core
,CD
4an
da
neut
raliz
ing
antib
ody.
[Wya
tt(1
995)
]R
.W
yatt,
J.M
oore
,M
.A
ccol
a,E
.D
esja
rdin
,J.
Rob
inso
n,&
J.S
odro
ski.
Invo
lvem
ento
fthe
V1/
V2
varia
ble
loop
stru
ctur
ein
the
expo
sure
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
gp12
0ep
itope
sin
duce
dby
rece
ptor
bind
ing.
JV
irol6
9:57
23–5
733,
1995
.(M
edlin
e:95
3639
86)N
otes
:Del
etio
nsin
the
V1/
V2
loop
sof
gp12
0re
sulte
din
the
loss
ofth
eab
ility
ofsC
D4
toin
duce
bind
ing
ofth
eM
Abs
17b,
48d,
and
A32
.A32
can
indu
cebi
ndin
gof
17b
and
48d;
this
indu
ctio
ndo
esno
tapp
ear
toin
volv
eth
eV
1/V
2re
gion
s.
[Wya
tt&
Sod
rosk
i(199
8)]
R.
Wya
tt&
J.S
odro
ski.
The
HIV
-1en
velo
pegl
y-co
prot
eins
:fus
ogen
s,an
tigen
s,an
dim
mun
ogen
s.S
cie
nce
280:
1884
–188
8,19
98.
(Med
line:
9829
6351
)N
otes
:R
evie
wdi
scus
sing
ofth
em
echa
nism
sus
edby
the
viru
sto
evad
ea
neut
raliz
ing
antib
ody
resp
onse
whi
lem
aint
ain-
ing
vita
lEnv
func
tions
ofbi
ndin
gto
targ
etce
lls,a
ndth
enen
terin
gth
roug
hm
embr
ane
fusi
on.
[Wya
tt(1
993)
]R
.Wya
tt,N
.Sul
livan
,M.T
hali,
H.R
epke
,D.H
o,J.
Rob
inso
n,M
.P
osne
r,&
J.S
odro
ski.
Fun
ctio
nal
and
Imm
unol
ogic
Cha
ract
eriz
atio
n
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-47
DE
C20
00
ofH
uman
Imm
unod
efici
ency
viru
sty
pe1
enve
lope
glyc
opro
tein
sco
ntai
n-in
gde
letio
nsof
the
maj
orva
riabl
ere
gion
s.JV
irol
67:4
557–
4565
,19
93.
(Med
line:
9332
3196
)N
otes
:Affi
nity
ofne
utra
lizin
gM
Abs
dire
cted
agai
nst
the
CD
4bi
ndin
gsi
tew
asin
crea
sed
dram
atic
ally
byde
letio
nm
utan
tsac
ross
the
V1/
V2
and
V3
stru
ctur
es,
sugg
estin
gth
atth
ese
dom
ains
mas
kth
ese
cons
erve
ddi
scon
tinuo
usep
itope
s.
[Wya
tt(1
992)
]R
.W
yatt,
M.
Tha
li,S
.T
illey
,A
.P
inte
r,M
.P
osne
r,D
.H
o,J.
Rob
inso
n,&
J.S
odro
ski.
Rel
atio
nshi
pof
the
hum
anim
mun
odefi
cien
cyvi
rus
type
1gp
120
third
varia
ble
loop
toel
emen
tsof
the
CD
4bi
ndin
gsi
te.
JV
irol6
6:69
97–7
004,
1992
.(M
edlin
e:93
0596
44)N
otes
:Thi
spa
pere
xam
ines
mut
atio
nsw
hich
alte
rM
Ab
bind
ing
and
neut
raliz
atio
n.A
nti-V
3M
Ab
9284
has
enha
nced
bind
ing
due
toa
mut
atio
nin
the
C4
regi
onth
atis
also
impo
rtan
tfo
rC
D4
bind
ing,
and
anti-
CD
4bi
ndin
gM
Abs
F10
5,1.
5ean
d11
25H
show
incr
ease
dpr
ecip
itatio
nof
agp
120
from
whi
chth
eV
3lo
opw
asde
lete
d,re
lativ
eto
wild
type
,in
RIP
Abu
ffer
cont
aini
ngno
n-io
nic
dete
rgen
ts.
[Xia
o(2
000a
)]Y.
Xia
o,M
.Lia
o,Y.
Lu,M
.P.D
ieric
h,&
Y.H
.Che
n.E
pito
pe-
vacc
ines
:a
new
stra
tegy
toin
duce
high
leve
lsof
neut
raliz
ing
antib
odie
sag
ains
tHIV
-1.Im
mu
no
bio
log
y201
:323
–31,
2000
a.(M
edlin
e:20
2365
47).
[Xia
o(2
000b
)]Y.
Xia
o,Y.
Zha
o,Y.
Lu,&
Y.H
.Che
n.E
pito
pe-v
acci
nein
duce
shi
ghle
vels
ofE
LDK
WA
-epi
tope
-spe
cific
neut
raliz
ing
antib
ody.Im
mu
no
lIn
vest
29:4
1–50
,200
0b.
(Med
line:
2017
3079
).
[Xu
(199
1)]
J.-Y
.X
u,M
.K
.G
orny
,T.
Pal
ker,
S.
Kar
wow
ska,
&S
.Z
olla
-P
azne
r.E
pito
pem
appi
ngof
two
imm
unod
omin
ant
dom
ains
ofgp
41,
the
tran
smem
bran
epr
otei
nof
hum
anim
mun
odefi
cien
cyvi
rus
type
1,us
ing
ten
hum
anm
onoc
lona
lan
tibod
ies.J
Viro
l65
:483
2–48
38,
1991
.(M
edlin
e:91
3330
26)
Not
es:
The
imm
unod
omin
ance
oflin
ear
epito
pein
the
regi
on59
0-60
0of
gp41
(clu
ster
I)w
ases
tabl
ishe
d,an
da
seco
ndco
nfor
mat
iona
lep
itope
was
map
ped
that
reac
ted
with
are
gion
betw
een
amin
oac
ids
644
and
663
(clu
ster
II).T
itrat
ion
expe
rimen
tssh
owed
that
ther
ew
as10
0-fo
ldm
ore
antib
ody
tocl
uste
rIt
han
clus
ter
IIin
patie
ntse
ra.
[Yam
ada
(199
1)]
M.
Yam
ada,
A.
Zur
brig
gen,
M.
B.
A.
Old
ston
e,&
R.
S.
Fuj
inam
i.C
omm
onim
mun
olog
icde
term
inan
tbe
twee
nhu
man
imm
unod
-efi
cien
cyvi
rus
type
1gp
41an
das
troc
ytes
.J
Viro
l65
:137
0–13
76,
1991
.(M
edlin
e:91
1407
28).
[Yan
g(1
998)
]G
.Yan
g,M
.P.D
’Sou
za,&
G.N
.Vya
s.N
eutr
aliz
ing
antib
od-
ies
agai
nst
HIV
dete
rmin
edby
ampl
ifica
tion
ofvi
rall
ong
term
inal
repe
at
sequ
ence
sfr
omce
llsin
fect
edin
vitr
oby
nonn
eutr
aliz
edvi
rions
.J
Acq
uir
Imm
un
eD
efic
Syn
drH
um
Re
trov
irol
17:2
7–34
,199
8.(M
edlin
e:98
0972
55)
Not
es:A
neut
raliz
atio
nas
say
was
deve
lope
dba
sed
onhe
min
este
dP
CR
am-
plifi
catio
nof
the
LTR
(HN
PC
R)
–LT
R-H
NP
CR
cons
iste
ntly
reve
aled
HIV
DN
Aan
dw
assh
own
tobe
ara
pid,
spec
ific
and
relia
ble
neut
raliz
atio
nas
say
base
don
test
sw
ith6
MA
bsan
d5
HIV
isol
ates
.
[Yan
g(1
997)
]W
.-P.
Yan
g,K
.G
reen
,S
.P
inz-
Sw
eene
y,A
.T.
Brio
nes,
D.
R.
Bur
ton,
&C
.F.B
arba
sIII
.C
DR
wal
king
mut
agen
esis
for
the
affin
itym
at-
urat
ion
ofa
pote
nthu
man
anti-
HIV
-1an
tibod
yin
toth
epi
com
olar
rang
e.J
Mo
lBio
l254
:392
–403
,199
7.(M
edlin
e:96
0957
99).
[Yos
hida
(199
7)]
K.Y
oshi
da,M
.Nak
amur
a,&
T.O
hno.
Mut
atio
nsof
the
HIV
type
1V
3lo
opun
der
sele
ctio
npr
essu
rew
ithne
utra
lizin
gm
onoc
lona
lant
i-bo
dyN
M-0
1.A
IDS
Re
sH
um
Re
trov
iru
ses13:1
283–
1290
,199
7.(M
edlin
e:93
3984
5).
[Yos
hiya
ma
(199
4)]
H.Y
oshi
yam
a,H
.-M
.Mo,
J.P.
Moo
re,&
D.D
.Ho.
Cha
r-ac
teriz
atio
nof
mut
ants
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
that
have
esca
ped
neut
raliz
atio
nby
mon
oclo
nala
ntib
ody
G3-
4to
the
gp12
0V
2lo
op.
JV
irol6
8:97
4–97
8,19
94.
(Med
line:
9411
8447
)N
otes
:M
Ab
G3-
4bi
nds
aco
nfor
mat
iona
llyse
nsiti
veep
itope
inth
eV
2lo
opof
HIV
-1R
F.R
Fw
ascu
lture
din
the
pres
ence
ofG
3-4
tose
lect
forn
eutr
aliz
atio
nre
sist
ance
.Thr
eein
depe
nden
texp
erim
ents
yiel
ded
esca
pem
utan
ts,a
ndse
quen
cing
reve
aled
two
V2
mut
atio
nsto
bere
spon
sibl
efo
rthe
neut
raliz
atio
nes
cape
phen
otyp
e,17
7Y
/Han
d17
9L/
P.E
xper
imen
tali
ntro
duct
ion
ofth
e17
9P
subs
titut
ion
resu
lted
inno
n-vi
able
viru
s,an
d17
7H
confi
rmed
the
resi
stan
ceph
enot
ype.
[Yu
(200
0)]
T.Yu
,Y.
Bai
,M
.P.
Die
rich,
&Y.
H.
Che
n.In
duct
ion
ofhi
ghle
vels
ofep
itope
-spe
cific
antib
odie
sby
epito
pe/p
eptid
eca
ndid
ate
vacc
ines
agai
nsth
uman
imm
unod
efici
ency
viru
sty
pe-1
(HIV
-1)[
InP
roce
ssC
itatio
n].
Mic
rob
iolI
mm
un
ol4
4:10
5–10
,200
0.(M
edlin
e:20
2606
33).
[Zin
ckgr
af(1
999)
]J.
W.Z
inck
graf
,J.M
.Win
chel
l,&
L.K
.Silb
art.
Ant
ibod
yre
spon
ses
toa
muc
osal
lyde
liver
edH
IV-1
gp12
0-de
rived
C4/
V3
pept
ide.
JR
ep
rod
Imm
un
ol45
:99–
112,
1999
.(M
edlin
e:20
1374
44).
[Zol
la-P
azne
r(1
997)
]S
.Z
olla
-Paz
ner,
C.
Alv
ing,
R.
Bel
she,
P.B
erm
an,
S.
Bur
da,
P.C
higu
rupa
ti,M
.L.
Cle
men
tsM
L,A
.M
.D
ulie
ge,
J.L.
Ex-
cler
,C
.H
ioe,
J.K
ahn,
M.
J.M
cElra
th,
S.
Sha
rpe,
F.S
inan
gil,
K.
Ste
imer
,M
.C
.W
alke
r,N
.W
asse
f,&
S.
Xu.
Neu
tral
izat
ion
ofa
clad
eB
prim
ary
isol
ate
byse
rafr
omhu
man
imm
unod
efici
ency
viru
s-un
infe
cted
reci
pien
ts
Ant
ibod
yR
efer
ence
sB Cell
IV-D
-48
DE
C20
00
ofca
ndid
ate
AID
Sva
ccin
es.J
Infe
ctD
is17
5:76
4–77
4,19
97.
(Med
line:
9724
0668
)Not
es:C
omm
enti
n:J
Infe
ctD
is19
97N
ov;1
76(5
):14
10-2
.Cla
deB
prim
ary
isol
ate
BZ
167
was
neut
raliz
ed,
usin
ga
new
assa
y,by
sera
from
HIV
-uni
nfec
ted
volu
ntee
rsin
vacc
ine
tria
ls.
[Zol
la-P
azne
r(1
999a
)]S
.Z
olla
-Paz
ner,
M.
K.
Gor
ny,
&P.
N.
Nya
mbi
.T
heim
plic
atio
nsof
antig
enic
dive
rsity
for
vacc
ine
deve
lopm
ent.
Imm
un
olL
ett
66:1
59–6
4,19
99a.
(Med
line:
9921
7699
).
[Zol
la-P
azne
r(1
999b
)]S
.Z
olla
-Paz
ner,
M.
K.
Gor
ny,
P.N
.N
yam
bi,
T.C
.Va
nCot
t,&
A.N
adas
.Im
mun
otyp
ing
ofhu
man
imm
unod
efici
ency
viru
sty
pe1
(HIV
):an
appr
oach
toim
mun
olog
iccl
assi
ficat
ion
ofH
IV.
JV
irol7
3:40
42–
51,
1999
b.(M
edlin
e:99
2143
43)
Not
es:
21hu
man
anti-
V3
MA
bsw
ere
stud
ied
with
resp
ectt
ocr
oss-
clad
ere
activ
ityan
dim
mun
olog
ical
rela
tions
hip
toot
her
hum
anan
ti-V
3M
Abs
.Bro
adcr
oss-
reac
tiviti
esw
ere
obse
rved
,and
V3
pept
ides
wer
egr
oupe
din
toim
mun
otyp
esth
atco
ntai
ned
pept
ides
from
seve
ralc
lade
s.
[Zol
la-P
azne
r(1
995)
]S
.Z
olla
-Paz
ner,
J.O
’Lea
ry,
S.
Bur
da,
M.
K.
Gor
ny,
M.
Kim
,J.
Mas
cola
,&
F.M
cCut
chan
.S
erot
ypin
gof
prim
ary
hum
anim
-m
unod
efici
ency
viru
sty
pe1
isol
ates
from
dive
rse
geog
raph
iclo
catio
nsby
flow
cyto
met
ry.J
Viro
l69:
3807
–381
5,19
95.
(Med
line:
9526
4474
)N
otes
:A
seto
f13
hum
anM
Abs
toa
varie
tyof
epito
pes
wer
ete
sted
agai
nsta
pane
lof
prim
ary
isol
ates
ofH
IV-1
,rep
rese
ntin
gdi
ffere
ntge
netic
clad
es.T
heV
3lo
opte
nded
tobe
Bcl
ade
rest
ricte
d,an
da
sing
legp
120
C-t
erm
inus
bind
ing
antib
ody
was
clad
esp
ecifi
c.Tw
oot
herg
p120
C-t
erm
inus
bind
ing
antib
odie
sw
ere
grou
psp
ecifi
c.
[Zol
la-P
azne
r&
Sha
rpe(
1995
)]S
.Z
olla
-Paz
ner
&S
.S
harp
e.A
rest
ing
cell
assa
yfo
rim
prov
edde
tect
ion
ofan
tibod
y-m
edia
ted
neut
raliz
atio
nof
HIV
type
1pr
imar
yis
olat
es.AID
SR
es
Hu
mR
etr
oviru
ses11:1
449–
1458
,199
5.(M
edlin
e:96
2884
43).
[Zvi
(199
7)]
A.Z
vi,D
.J.F
eige
lson
,Y.H
ayek
,&J.
Ang
liste
r.C
onfo
rmat
ion
ofth
epr
inci
paln
eutr
aliz
ing
dete
rmin
anto
fhum
anim
mun
odefi
cien
cyvi
rus
type
1in
com
plex
with
anan
ti-gp
120
viru
sne
utra
lizin
gan
tibod
yst
udie
dby
two-
dim
ensi
onal
nucl
ear
mag
netic
reso
nanc
edi
ffere
nce
spec
tros
copy
.B
ioch
em
istr
y36:
8619
–27,
1997
.(M
edlin
e:97
3619
73).
[Zvi
(199
5a)]
A.
Zvi
,I.
Kus
tano
vich
,D
.F
eige
lson
,R
.Le
vy,
M.
Eis
enst
ein,
S.
Mat
sush
ita,
P.R
icha
let-
Sec
orde
l,M
.H
.R
egen
mor
tel,
&J.
Ang
liste
r.
NM
Rm
appi
ngof
the
antig
enic
dete
rmin
antr
ecog
nize
dby
anan
ti-gp
120,
hu-
man
imm
unod
efici
ency
viru
sne
utra
lizin
gan
tibod
y.E
urJ
Bio
che
m229
:178
–18
7,19
95a.
(Med
line:
9526
2664
).
[Zvi
(199
5b)]
A.Z
vi,I
.Kus
tano
vich
,Y.H
ayek
,S.M
atsu
shita
,&J.
Ang
liste
r.T
hepr
inci
pal
neut
raliz
ing
dete
rmin
ant
ofH
IV-1
loca
ted
inV
3of
gp12
0fo
rms
a12
-res
idue
loop
byin
tern
alhy
drop
hobi
cin
tera
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