Vaccines

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Vaccines

• Protection by prior immunisation from the latin
  vacca a cow. Introduced by Jenner 1796.
• The triumphant extermination of small pox or is
  it ?

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Vaccines in routine paediatric or adult use
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Diptheria, tetanus and pertussis (DPT)

• Sub-unit vaccines aimed at bacterial components
  with inherent toxicity.

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• Mechanisms of protection toxin neutralisation.

If toxin binds its receptor, pathology results
If toxin binds antibody, it cant bind receptor,
and the complex is then harmlessly disposed of.
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• The degree of protection is simply related to the
  amount and the affinity of antibody present at
  time of exposure.

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• DPT is given first at 4-6 months of age.
• Subunit vaccines are inert and therefore low risk
  (providing manufacturing quality is high).
• Effectiveness is very high gt 90.
• Antibody titres remain high for 5-10 years need
  boosters.

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Subunit vaccines require adjuvant in the form of
alum (aluminium salts).
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Adjuvants

• Depot effect slow release
• Activation of innate immunity.

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Other vaccines which work on the same principles
as DPT.
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Polio vaccine

• Two forms used for universal paediatric
  vaccination live attenuated (Sabine) and killed
  (SalK)
• Both effective and work by antibody-mediated
  virus neutralisation.
• May well both be replaced by recombinant surface
  coat protein in the next few years (see
  hepatitis B).

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Mechanism of viral neutralisation
VIRAL CAPSID
If virus binds its receptor, enters cell and
causes disease.
If virus binds antibody, it cant bind receptor,
and the complex is then harmlessly disposed of.
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Hepatitis B

• Recombinant surface protein of virus
• Protects by antibody-mediated viral
  neutralisation
• Very effective but only used currently on high
  risk groups.

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Measles , mumps and rubella (MMR)

• All three are live attenuated viruses

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Mechanisms of protection

• Antibody neutralisation (as above)
• Cellular cytotoxicity

CD8 T cell
Cytotoxic cell killing interrupts viral
replication
Once virus is intracellular, it can replicate and
is protected from neutralising antibody.
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Attenuated micro-organisms

• Strains selected (usually after prolonged in
  vitro culture) because they do not cause disease.
• MAY still cause disease in the immuno-compromised
  host.
• MAY revert to wild-type (e.g. by genetic
  recombination).
• Are more difficult for quality control.

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However, live vaccines are still necessary

• Generate stronger immunity.
• Dead vaccines are poor stimulators of cytotoxic T
  cells
• Alum is a very poor adjuvant for cellular
  immunity (TH1), but no other adjuvants are
  licensed for use in humans.

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There is no scientifically credible evidence that
measles vaccine, either in the context of MMR or
alone, is connected to autism.
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BCG and tuberculosis

• Live attenuated Mycobacterium bovis (bovine
  tuberculosis).
• Protects via T-cell mediated macrophage
  activation.

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T cell dependent macrophage killing.
Mycobacterium tuberculosis is resistant to
killing by resting macrophages, and multiplies
within them.
Activated macrophages kill M. tb via reactive
oxygen and other toxic products.
Macrophage
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• Effectiveness of BCG is limited and dependent on
  geographical location.
• Nevertheless, now given universally as single
  dose paediatric vaccine, sometimes very young
  indeed.

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Vaccination and the prevention of meningitis

• Major causes of meningitis were Haemophilus
  influenziae (Hib) and meningococcus. Also S.
  pneumoniae sometimes.
• Vaccines made of polysaccharide (from multiple
  strains) protective via opsonisation, and
  complement activation.

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Bacteria coated with antibody/complement are
taken up and destroyed by neutrophils.
Encapsulated bacteria are resistant to
phagocytosis
Phagocytic neutrophils
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Polysaccarides as antigens

• T cell independent antigens.
• Mostly IgM response.
• No memory, affinity maturation, isotype switching
• Very poor in children under the age of 6 months
  (high risk group).

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Conjugate vaccines

• Hib introduced in early 90s.
• Meningococcus group C conjugate introduced in
  1999.
• Conjugates of polysaccharide capsule with tetanus
  or diphteria toxin.
• Converts a T-independent response to a T
  dependent one. Clever immunologists !

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Over the horizon

• No vaccine for HIV.
• No vaccine for any eukaryotic parasite.
• Limited vaccine for tuberculosis.
• No real therapeutic vaccines.
• No vaccines for cancer.
• IMMUNOLOGISTS NEED TO KEEP WORKING.