Vaccines Polio - close to eradication. In 2001 >1000 cases worldwide; last wild case in Americas in...
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Transcript of Vaccines Polio - close to eradication. In 2001 >1000 cases worldwide; last wild case in Americas in...
VaccinesVaccines
Polio - close to eradication. In 2001 >1000 cases worldwide; last wild case in
Americas in Peru in 1991
Learning objectivesLearning 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
Outcomes of immunizationOutcomes 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
Vaccines have saved lives and reduced cases
Ideal VaccineIdeal Vaccine
• Safe
• Inexpensive
• Heat-stable
• Oral administration
• Effective in all ages
• Single dose
• All strains sensitive
• Induces systemic and mucosal immunity - CMI and antibody
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?
Eradication of smallpoxEradication of smallpox
1) No animal reservoir2) Lifelong immunity(no antigenic shift or drift)3) Subclinical cases rare4) Infectivity does not precede overt symptoms5) One Variola serotype (monotypic vs heterotypic)6) Effective vaccine7) Major commitment by governments to
surveillance and containment (length of incubation period)
Types of vaccinesTypes 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
Polio eradicationPolio eradication
• Cases in Dominican Republic and Haiti 2000/01
• 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
For each type of vaccine
• Advantages • Disadvantages
Can an HIV vaccine Can an HIV vaccine be effective?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
HPV Type 11 vaccineHPV 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
Lancet Nov. 2004 Bivalent vaccine L1 Lancet Nov. 2004 Bivalent vaccine L1 VLPS to HPV16/18VLPS to HPV16/18
Clinical Trials - Would you volunteer?
http://www.clinicaltrials.gov/