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LOGO
11.VACCINE
TIANA MILANDA
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What is a vaccine ?
A preparation of bacteria, viruses,
parasites designed to elicit animmune response, therebyproviding protective immunityagainst a potential pathogen.
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Passive vs ActiveImmunity
Passive Immunity Immunity due by thepresence in theirtissues of antibody orprimed lymphocytes
derived from anotherimmune individual.
Active Immunity Protection due todevelopment of an
immune response in anindividual followingstimulation withantigen, e.g. in avaccine or duringinfection.
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Passive Immunization
Transfer of preformed antibodies or primedlymphocytes to a new recipient. Usually, horse serumor pooled human sera are used.
Transfer can occur naturally, through placenta, milkor colostrum (e.g. diphtheria, tetanus, rubeola,rubella, mumps, polio)
Transfer can occur manually, via injection ofantibodies into recipient
Passive immunization is performed in the followingsituations:
Recepient has congenital or acquired B cell defects When exposure is likely, or when time doesnt permit active
immunization
When disease is already present (e.g. tetanus, spider/snake bites)
Risks include anti-isotype or anti-allotype responses
in recipients
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Active Immunization
Intentional induction of protective immunityand immunological memory
Can be mediated by infection withmicroogranism, or vaccination
Vaccinations frequently require boosters,subsequent vaccinations to boost theimmune response to a particular pathogen:
Passively acquired maternal antibodies may interferewith vaccination process
Multiple exposures may be necessary to adequatelyimmunize against all strains/epitopes
Memory T cell population may decline with age
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Fig. 18-3
Immune Response
To Polio Vaccine
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Immunization schedule for infants and children
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History
Greek physicians noticedthat people who survivedsmallpox never got itagain.
The insight: Becominginfected by certaindiseases gives immunity.
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Smallpox
Mummies
China/India Crusaders
West Europe: fatality rate 25%
History changed:
Cortes
Louis XIV
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Smallpox
Vaccination
Jenner 1796 :Cowpox/Swinepox
1800s : compulsory
childhood vaccination 1930s : last natural UK
case
1940s : last natural US case 1958 : WHO program October 1977: Last case
(Somalia)
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Types Of Vaccines
Whole Organism Vaccines Attenuated (non-virulent) viral or bacterial vaccines
Inactivated (killed) viral or bacterial vaccines
Purified Macromolecule Vaccines
Toxoid Vaccines (e.g. tetanus, diphtheria)
Polysaccharide Vaccines (e.g. S. pneumoniae, Hib)
Recombinant Antigen Vaccines (e.g. HBsAg)
Recombinant Vector Vaccines
DNA Vaccines
Synthetic Peptide Vaccines
Multivalent Subunit Vaccines
Li Att t d V i
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Live Attenuated Vaccines
Attenuated (weakened) form of the
"wild" virus or bacteriumViral measles, mumps,
rubella, vaccinia,varicella/zoster,
yellow fever, rotavirus,intranasal influenza,oral polio (Sabin)
Bacterial BCG (TB), oral
typhoid
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Inactivated Vaccines
Virulent pathogen is inactived by chemical
or irradiations
Viral polio (Salk),
hepatitis A,rabies, influenza
Bacterial pertussis,typhoid, cholera
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Sabin Polio Vaccine Attenuated by passage in foreign host (monkey kidney
cells)
Selection to grow in new host makes virus less suited tooriginal host
Grows in epithelial cells, does not grow in nerves
50% vaccinees feces, 50% contacts
Vaccine-associated cases: revertants
1 In 4,000,000 vaccine infections paralytic polio
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Salk Polio Vaccine
Formaldehyde-fixed
No reversion
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Polio Vaccine
Why use the Sabin vaccine?
Local immunity: vaccine virus just like naturalinfection
Stopping replication in G.I. tract stops viralreplication TOTALLY
No problem with selective inactivation
Life-long immunity
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Reciprocalvirusantibody
titer
512
128
32
8
2
1
SerumIgG
SerumIgG
Serum IgM SerumIgM
Nasal andduodenal IgA
NasalIgASerum
IgA
SerumIgA
DuodenalIgA
DaysVaccination Vaccination
4
8
4896 96
Killed(Salk)Vaccine
Live
(Sabin)Vaccine
Live virus generates a more complete immune response
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Types Of Vaccines
Whole Organism Vaccines Attenuated (non-virulent) viral or bacterial vaccines
Inactivated (killed) viral or bacterial vaccines
Purified Macromolecule Vaccines Polysaccharide Vaccines (e.g. S. pneumoniae, Hib)
Toxoid Vaccines (e.g. tetanus, diphtheria)
Recombinant Antigen Vaccines (e.g. HBsAg)
Recombinant Vector Vaccines
DNA Vaccines
Synthetic Peptide Vaccines
Multivalent Subunit Vaccines
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Clone gene from virus or bacteriaand express this protein antigen in
yeast, bacteria or mammalian cellsin culture
Recombinant Antigen Vaccines
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Recombinant Antigen Vaccines
Pluses
Easily manufactured and often relatively stable
Cannot revert to recreate pathogen
Minuses Poorly immunogenic
Post-translational modifications
Poor T cell response
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Types Of Vaccines
Whole Organism Vaccines Attenuated (non-virulent) viral or bacterial vaccines
Inactivated (killed) viral or bacterial vaccines
Purified Macromolecule Vaccines Polysaccharide Vaccines (e.g. S. pneumoniae, Hib)
Toxoid Vaccines (e.g. tetanus, diphtheria)
Recombinant Antigen Vaccines (e.g. HBsAg)
Recombinant Vector Vaccines
DNA Vaccines
Synthetic Peptide Vaccines
Multivalent Subunit Vaccines
R bi V V i
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Recombinant Vector Vaccines
Clone gene from virus or bacteria into genome of anothervirus (adenovirus, canary pox, vaccinia)
And use this live virus as vaccine
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Recombinant Vector VaccinesPluses
Infects human cells but some do not replicate Better presentation of antigen
Generate T cell response
Minuses
Can cause bad reactions
Can be problems with pre-exisiting immunity to virus
Often can only accommodate one or two antigens
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Fig. 18-6
DNA
Vaccines
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DNA Vaccines Plasmids are easily manufactured in largeamounts
DNA is very stable. DNA resists temperatureextremes so storage and transport
DNA sequence can be changed easily in the
laboratory. This means that we can respond tochanges in the infectious agent By using the plasmid in the vaccine to code forantigen synthesis, the antigenic protein(s) that are
produced are processed in the same way as theproteins of the virus.
Mixtures of plasmids could be used that encodemany protein fragments from a virus/viruses a
broad spectrum vaccine
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DNA Vaccines
Possible Problems
Potential integration of plasmid into host genomeleading to insertional mutagenesis
Induction of autoimmune responses (e.g.pathogenic anti-DNA antibodies)
Induction of immunologic tolerance (e.g. where
the expression of the antigen in the host may leadto specific non-responsiveness to that antigen)
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antibody
Synthetic peptide vaccines
Anti-idiotype vaccine
epitope
Antibody with
epitope bindingsite
Virus
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antibody
Make antibodyagainst antibodyidiotype
Anti-idiotypeantibody
Anti-idiotypeantibody mimicsthe epitope
Synthetic peptide vaccines
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Anti-anti-idiotypeantibody
Antibody to anti-idiotypeantibody
Binds and neutralizesvirus
Anti-idiotypeantibody
Anti-anti-idiotypeantibody
Anti-anti-idiotypeantibody
Use as vaccine
Synthetic peptide vaccines
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Multivalent
SubunitVaccines
Fig. 18-7
Multivalent subunit vaccine
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Influenza Vaccine
Trivalent
Efficacy
Immunity
Schedule
Type A (2) and type B (1)
Varies depending on circulatingstrain, age, and underlyingillness
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Ideal Vaccine
Safe
InexpensiveHeat-stable
Oral administration
Effective in all ages
Single dose
All strains sensitive
Induces systemic
and mucosalimmunity CTL andantibody
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What knowledge is needed toproduce a vaccine ?
1. Understand lifecycle of pathogen find best target stage.
2. Understand immune mechanisms stimulatedby parasite humoral /cellular response ?
3. Understanding the incubation period of thepathogen.
A short incubation period (e.g. influenza)results in symptoms before memory cells are
activated. Circulating antibodies are importantin these instances.
Longer incubation periods (e.g. polio) allowmemory cells to become activated prior to
onset of symptoms
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HIV: Virion (Virus Particle)
gp120
gp41
viral e nvelopeglycoproteins
lipid
membrane ofenvelope
(host derive d)
matrix (p17)
viral core(p24)
reverse
transcriptase
viral RNA (ss)(2 copie s)
HIV Virion Structure
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HIV Lifecycle
T Cell
CD4
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X
Reverse TranscriptionInhibitors
Protease Blockers
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HIV Vaccine Approaches
Protein subunit
Synthetic peptide
Naked DNA
Inactivated Virus
Live-attenuatedVirus
Live-vectored Vaccine
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Old Technology:
Grow in animals (vacciniain calves for smallpox;rabbit brains for rabies)
Simple bacterial culture
(Cholera vibrio) theninactivation
Grow in eggs (influenza,vaccinia) then inactivate
>100 million eggs used forinfluenza in the USA every year
Vaccine Technology
i h l
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Vaccine Technology
Newer Technology:
Mammalian cell culture: live and killedvaccines
Subunit vaccines:
From serum (HBV) or virus / bacterial disruption Made via recombinant DNA technology
Recombinant vaccine vectors
DNA vaccines
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Anti-anti-idiotypeantibody
Antibody to anti-idiotypeantibody
Binds and neutralizesvirus
Anti-idiotypeantibody
Anti-anti-idiotypeantibody
Anti-anti-idiotypeantibody
Use as vaccine
Vaccine Technology
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Thank you!