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Chapter 18 Vaccines

Chapter 18 Vaccines

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Chapter 18 Vaccines

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  1. 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!

  2. 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!

  3. 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

  4. 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

  5. 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

  6. Childhood vaccines • 7 major vaccines: • HepB • DTaP • IPV • MMR • Hib • Var • PCV *children require booster shots for most… (American Academy of Pediatrics, 2002)

  7. 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

  8. 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

  9. 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

  10. 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

  11. “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

  12. “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)

  13. “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

  14. 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

  15. DNA vaccines: