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