Please read Chapters 5, 6and 7 of your vaccine text
for next Wednesday’slecture
Chapters 9, 17 and 8 fornext Friday’s lectures
Valerie Daggett
ppt files for first 2 lectures
Past exams
Principles of Vaccination
• Self vs. nonself
• Protection from infectious disease
• Usually indicated by the presenceof antibody
• Very specific to a single organism
Immunity
Principles of Vaccination
• Protection produced by the person'sown immune system
• Usually permanent
• Protection transferred from anotherperson or animal
• Temporary protection that waneswith time
Active Immunity
Passive Immunity
Principles of Vaccination
• A live or inactivated substance(e.g., protein, polysaccharide)capable of producing an immuneresponse
• Protein molecules (immuno-globulin) produced by Blymphocytes to help eliminate anantigen
Antigen
Antibody
3 main classes of antibodies
IgG blood monomer
IgM muscle/blood pentamer
sIgAmucosal surface dimer
Not all immune responses are equal
IgG may not be all that effective for
something colonizing the intestines or
nasal passages
Constant Region
Hypervariable
Region
Light
Chain
Heavy
Chain
Antigen
Binding Region
Structure of an anti-influenza
hemagglutinin antibody
Hemagglutinin
Structure of an
influenza hemagglutinin-
antibody complex
Human antibody
Rotate ~90°
Add all atoms
Binding surface of hemagglutinin-
antibody complex
Antigen residues
at the interface
= epitope
Interface of hemagglutinin-
antibody complex
Epitopes are
typically ~5
residues long
hemagglutinin
antibody
Space-filling mode
Grey now = mainchain
of hemagglutinin
Epitopes reside in
turns and loops
Interface of influenza
hemagglutinin-antibody complex
Passive Immunity
• Transfer of antibody produced byone human or other animal toanother
• Temporary protection (weeks –months)
• Transplacental most importantsource in infancy
Sources of Passive Immunity
• Almost all blood or blood products
• Homologous pooled human antibody(HepA, measles)
• Homologous human hyperimmuneglobulin (HepB, tetanus, varicella,rabies)
• Heterologous hyperimmune serum(antitoxin-diphtheria, botulism)
Passive Immunization
• Polymeric vs Monomericantibodies
• IM preps---contain Ab aggregatesand other serum components
If given IV they can activatecomplement system
! anaphylaxis andcardiovascular collapse
Passive Immunization
• IV preps --- stabilizers added togive monomeric IgG
Okay in blood stream
Vaccination
• Active immunity produced byvaccine
• Immunity and immunologicmemory similar to naturalinfection but without risk ofdisease
(transparency)
Classification of Vaccines
• Live attenuated
– viral
– bacterial
• Inactivated
Inactivated Vaccines
• viruses• bacteria
• protein-based– toxoid– subunit
• polysaccharide-based– pure– conjugate
Whole
Fractional
Principles of Vaccination
General Rule
The more similar a vaccine is to
the disease-causing form of the
organism, the better the
immune response to the
vaccine.
Live Attenuated Vaccines
• Attenuated (weakened) form ofthe "wild" virus or bacterium
• Must replicate to be effective
• Immune response similar tonatural infection
• Usually effective with one dose*
*except those administered orally
Live Attenuated Vaccines
• Severe reactions possible
• Interference from circulatingantibody
• Fragile – must be stored andhandled carefully
Live Attenuated Vaccines
• Viral measles, mumps,rubella, vaccinia, varicella/zoster, yellow fever, rotavirus, intranasal influenza, oral polio*
• Bacterial BCG, oral typhoid
*not available in the United States
Inactivated Vaccines
• Cannot replicate
• Generally not as effective as livevaccines
• Less interference from circulatingantibody than live vaccines
• Generally require 3-5 doses
• Immune response mostly humoral
• Antibody titer may diminish with time
Inactivated Vaccines
• Viral polio, hepatitis A,rabies, influenza*
• Bacterial pertussis*, typhoid*cholera*, plague*
Whole-cell vaccines
*not available in the United States
Inactivated Vaccines
• Subunit hepatitis B, influenza,acellular pertussis,human papillomavirus,anthrax, Lyme*
• Toxoid diphtheria, tetanus
Fractional vaccines
*not available in the United States
Pure Polysaccharide Vaccines
• Not consistently immunogenic inchildren younger than 2 years ofage
• No booster response
• Antibody with less functionalactivity
• Immunogenicity improved byconjugation
Polysaccharide Vaccines
• pneumococcal
• meningococcal
• Salmonella Typhi (Vi)
• Haemophilus influenzae type b
• pneumococcal
• meningococcal
Pure polysaccharide
Conjugate polysaccharide
Principles of Vaccination
General Rule
Inactivated vaccines are generally not
affected by circulating antibody to the
antigen.
Live attenuated vaccines may be
affected by circulating antibody to the
antigen.
Product Given First
Vaccine
Antibody
Action
Wait 2 weeks before
giving antibody
Wait 3 months or
longer before giving
vaccine (See Table, Appendix A)
Antibody and Measles- andVaricella-Containing
Vaccines
Principles of Vaccination
General Rule
All vaccines should be
administered at the same visit as
all other vaccines.
Intervals and Ages
• Vaccine doses should not beadministered at intervals less than theminimum intervals or earlier than theminimum age
• It is not necessary to restart the series or
add doses because of an extended interval
between doses
Vaccination doesn‘t count
Vaccination counts
Vaccine Adverse Reactions
• Local
– pain, swelling, redness at site of injection
– common with inactivated vaccines
– usually mild and self-limited
Vaccine Adverse Reactions
• Systemic
– fever, malaise, headache
– nonspecific
– may be unrelated to vaccine
Live Attenuated Vaccines
• Must replicate to produceimmunity
• Symptoms usually mild
• Occur after an incubation period(usually 7-21 days)
Vaccine Adverse Reactions
• Allergic
– due to vaccine or vaccine component
– rare
– risk minimized by screening
Vaccine Adverse Event Reporting System
(VAERS)
www.vaers.hhs.gov
Contraindication
• A condition in a recipient thatgreatly increases the chance of aserious adverse reaction
Precaution
• A condition in a recipient thatmight increase the chance orseverity of an adverse reaction,or
• Might compromise the ability ofthe vaccine to produce immunity
Contraindications and Precautions
• severe allergic reaction to a vaccinecomponent or following a prior dose
• encephalopathy not due to anotheridentifiable cause occurring within 7days of pertussis vaccination
Permanent contraindications tovaccination:
Vaccination of Pregnant Women
• Live vaccines should not beadministered to women known tobe pregnant
• In general inactivated vaccinesmay be administered to pregnantwomen for whom they areindicated
Vaccination ofImmunosuppressed Persons
• Live vaccines should not beadministered to severelyimmunosuppressed persons
• Inactivated vaccines are safe touse in immunosuppressedpersons but the response to thevaccine may be decreased
Immunosuppression
• Disease
• Chemotherapy
• Corticosteroids
Invalid Contraindicationsto Vaccination
• Mild illness
• Antimicrobial therapy
• Disease exposure or convalescence
• Pregnant or immunosuppressed person inthe household
• Breastfeeding
• Preterm birth
• Allergy to products not present in vaccine orallergy that is not anaphylactic
• Family history of adverse events
• Tuberculin skin testing
• Multiple vaccines
Vaccination During Acute Illness
• No evidence that acute illnessreduces vaccine efficacy orincreases vaccine adverse reactions
• Vaccines should be delayed until theillness has improved
• Mild illness, such as otitis media oran upper respiratory infection, isNOT a contraindication tovaccination