Vaccines

1
Vaccines

• Polio - close to eradication. In 2001 gt1000 cases
  worldwide last wild case in Americas in Peru in
  1991

2
Learning objectives

• Compare the attributes of available virus
  vaccines compare to the ideal vaccine
• Explain the advantages and disadvantages of the
  various types of virus vaccines
• Explain how smallpox was eradicated and why most
  other virus diseases cannot be eliminated with
  the same strategy

3
Outcomes of immunization

• Sterilizing immunity - gets virus before it can
  enter any cells
• Transient Infection - no symptoms
• Controlled infection - virus establishes and
  multiplies but does not spread
• Levels below transmissibility levels

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Vaccines have saved lives and reduced cases
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Ideal Vaccine

• Safe
• Inexpensive
• Heat-stable
• Oral administration
• Effective in all ages
• Single dose
• All strains sensitive
• Induces systemic and mucosal immunity - CMI and
  antibody

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Aimed at stimulating both humoral and CMI

• Antibody is primarily aimed at surface capsid or
  env proteins of free virus
• CMI can be aimed at internal proteins expressed
  with MHC1 and these may be more conserved among
  subtypes
• How do you measure each response?
• How do you measure protection?

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Eradication of smallpox

• 1) No animal reservoir
• 2) Lifelong immunity(no antigenic shift or drift)
• 3) Subclinical cases rare
• 4) Infectivity does not precede overt symptoms
• 5) One Variola serotype (monotypic vs
  heterotypic)
• 6) Effective vaccine
• 7) Major commitment by governments to
  surveillance and containment (length of
  incubation period)

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Types of vaccines

• Inactivated - formalin treatment
• Serum antibodies
• Can be used on immunodeficient patients
• Live-Attenuated - from nature or by passage in
  culture
• Polio
• Temp sensitive so poorer replication at 37
• IRES mutants
• Oral administration and IgA production

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Polio eradication

• Cases in Dominican Republic and Haiti 2000/01

10

• Subunit - gene cloning products (HBV)
• Peptide epitopes (FMD)
• Vaccinia/pox vector vaccines - replicates
• DNA vaccines - naked
• Pseudovirions - env protein of vaccine virus
• Replicons - non replicating virus carries gene
  from vaccine virus

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For each type of vaccine

• Advantages

• Disadvantages

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Can an HIV vaccine be effective?

• DNA vaccine for env/gag augmented with IL
• Challenge with SHIV
• 1 of 8 monkeys developed disease after 20 weeks
• Showed loss of CTL against a gag protein - single
  nucleotide escape mutant predominated
• Rapid emergence wins immune battle
• http//www.niaid.nih.gov/daids/vaccine/info.htm

13
HPV Type 11 vaccine

• Type 11 low risk but gives warts
• Capsid protein can assemble into VLP
• Immunize seronegative women with VLP and measure
  ab and CTL responses

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Lancet Nov. 2004 Bivalent vaccine L1 VLPS to
HPV16/18
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Clinical Trials - Would you volunteer?
http//www.clinicaltrials.gov/