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:
