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, > 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 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 polysaccharide recombinant 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: