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/