Chapter 18 Vaccines

• Termed coined by Pasteur to honor Jenner’s work

• Vaccines are cost-effective uses of our immune system

• Dramatic reduction of – Diptheria– Measles– Mumps – Pertussis– Polio – Tetanus

• No more naturally acquired cases of smallpox!

Still a significant need for new vaccines

• For other diseases: TB

malaria

HIV

• Increase safety of present vaccine, lower cost, and dissemination

• Road to vaccine development is long and laden with:– Side effects

– Exascerbation of disease state

– Acquisition of disease state!

Immunization:

Passive Immunity & Short-term protection

• Transient protection (remedy for current problem)

• Involves transfer of preformed Ig:– between ☥ and fetus (trans-placental) & colostrum

– Or by injection

• Given to those exposed to botulism, tetanus, diptheria, hepatitis, rabies, measles, snake/insect bites

• Provides immediate protection to healthcare/travellers

• Passive immunity does not activate IS! and produces no memory

Immunization:

Risks of Passive Immunity

If Antibody is produced in another spp, the human recipient can produce an IR vs it…

In some IgE production vs isotypic Ab -> systemic mast cell degran -> anaphylaxis

In others IgM or IgG vs isotype -> complement activation -> Type III Rxn

If human gammaglobulin results can be less severe

Immunization:

Active Immunization and Long-term protection

• Promotes protective immunity and imm memory• Is achieved by:

– Natural infection– Artificial intro of whole cells/antigens

• Immune system plays an ACTIVE role -> stim Ag-reactive T/B cells

• Immunizations have played a sig role in decrease of infect. disease –esp in children

• Yet, recent drop in immunization rates

Childhood vaccines• 7 major vaccines:

– HepB

– DTaP

– IPV

– MMR

– Hib

– Var

– PCV

*children require booster shots for most…

(American Academy of Pediatrics, 2002)

Adult vaccines (dep on risk group)

• For those living in close quarters/ immunity– Meningitis (Hib)

– Pneumonia (PCV)

– Influenza

• For travelers to endemic areas:– Cholera Meningits

– Typhus Yellow fever

– Typhoid Polio

– Hepatitis *Anthrax

Designing vaccines

Important questions to consider:

1- Which IS should be activated?

2- Is immunologic memory stimulated?

This depends on the disease.. Influenza has a short incubation (1-2 d) effective imm vs flu depends on maintaining hi levels of Ig through repeat immunizations

Polio virus has a longer incubation (>3d) gives memory cells time to produce serum Ig

Whole Organism Vaccines

1) Attenuated viruses and bacteria-can still grow to a degree w/i inoc. host

Positives:Provides prolonged IS exposure to epitopes> immunogenicity, > memoryTypically req. ONLY 1 shotStimulates host cell-mediated response

NegativesPoss. of reversion to virulent form and side effectsEx: Polio and Measles

Whole Organism Vaccines

2) Inactivated viruses and bacteria

-can be performed with heat or chemicals*

(formaldehyde, alkylating agents)

• Usually requires repeated boosters

• Predominantly humoral IR

• **risks of containing active pathogen

“Parts” – purified macromolecules as vaccines

Avoids the risks of the ‘whole org’ vaccines-3 forms: inactivated exotoxin

capsular polysacchariderecombinant MO antigens

1) Inact. exotoxin (“Toxoids”)-purify exotoxin, treat with formaldehyde-produces anti-toxin Ig which bind to toxin-exotoxin genes can be cloned/recombined in cells to produce

large quantities**used for diptheria and tetanus

“Parts” – purified macromolecules as vaccines

2) Capsular polysaccharides--Anti-phagocytic mechanism

-Vaccines using capsular components stim Ig prod

-Vaccines for Strep pneu, N. meningitidis -> purified polysacch injected subcutaneously to activate memory B cells and IgA response!

Can invoke Th activation if polysacch is added to protein carrier (Ex: Hib is cap polysacch linked to tetanus toxoid)

“Parts” – purified macromolecules as vaccines

3) Recombinant MO Antigens –

HepB surface Ag (HBsAg) – cloned in yeast

-may be able to produce large amts of vaccine this way!

-hope for 250 million+ carriers of chronic HepB worldwide

Recombinant Vector Vaccines

-Genes encoding significant Ag’s from pathogens may be transferred to attenuated viruses/bacteria

Vectors include: vaccinia, polio, adenoviruses

Salmonella, BCG strain of M. bovis, oral Strep

Other vectors may prove to be safer

DNA vaccines: