1. Vaccines Polio - close to eradication. In 2001 >1000 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

4. Vaccines have saved lives and reduced cases

5. 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

6. 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?

7. 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)

8. 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

9. 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

11. For each type of vaccine AdvantagesDisadvantages

12. 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

14. Lancet Nov. 2004 Bivalent vaccine L1 VLPS to HPV16/18

15. Clinical Trials - Would you volunteer? http://www.clinicaltrials.gov/