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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.

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chapter 18 vaccines
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
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
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
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
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
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
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
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
Whole Organism Vaccines
  • Attenuated viruses and bacteria

-can still grow to a degree w/i inoc. host

Positives:

Provides prolonged IS exposure to epitopes

> immunogenicity, > memory

Typically req. ONLY 1 shot

Stimulates host cell-mediated response

Negatives

Poss. of reversion to virulent form and side effects

Ex: Polio and Measles

whole organism vaccines10
Whole Organism Vaccines
  • 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
“Parts” – purified macromolecules as vaccines

Avoids the risks of the ‘whole org’ vaccines

-3 forms: inactivated exotoxin

capsular polysaccharide

recombinant MO antigens

  • 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 vaccines12
“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 vaccines13
“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
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