Transcript 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
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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:
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Cholera
Typhus
Typhoid
Hepatitis
Meningits
Yellow fever
Polio
*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: