INFLUENZA A periodic global threat

1. INFLUENZA A periodic global threat

2. Influenza vaccine MMWR 2003; 52:987-92 INFLUENZA: the leading cause of vaccine-preventable deaths in the United States

3. Influenza vaccine Four generations • Killed vaccine - past (present) • Split vaccine - present (future) • Live vaccine - (present) future • DNA vaccine - future (potential)

4. Influenza vaccinationof HCW at Schneider Parameter %reduction • Number sick 25% • Sickness events 35% • Fever >38.5 38% • Days sick 50%

5. Influenza vaccinationof >65y, Maccabi HO Shapiro, IMAJ 10/03 • Cohort of 84,613, 43% vaccinated • Vaccination: 30% reduction in hospitalizations 70% in mortality • NNT to prevent hospitalization: 53 • To prevent 1 hosp d in high risk group: 1 vaccine

6. Efficacy of live-attenuated influenza vaccine NEJM 1999; 338:1405-12 • 288 vaccinees, 2 doses (2m) • Monitored over influenza season • Culture-proven influenza: 14 vs 95 cases , efficacy 93% (88%-96%) 89% - one dose

7. Live-attenuated cold-adaptedreassorted influenza vaccine Childhood study in Israel • Double-blind, placebo-controlled study of 420 children (6m-3y) attending DCC followed 2 winters, after boosting • Culture-proven influenza: 13.4%-32.1%!!! • Efficacy: Influenza 82%-84% Influenza-associated AOM 91% Work missed 39%

8. INFLUENZA A periodic global threat • A new pandemic – WHEN?? • Vaccine:H1N1, H3N2,B • Hong Kong, S/E Asia, Holland • A/H5N1, H7N7

9. WHY DNA INFLUENZA VACCINE? • Genetic drift or shift - mutations in envelope proteins • DNA vaccine - nucleoprotein(core) or matrix genes, similar in many strains • Heterotypic protection • Lifelong protection • Induced cellular & humoral immunity

10. DNA VACCINE

11. DNA INFLUENZA VACCINE CMJ 1/04, Vaccine 2/03, EID 8/02 Heterotypic protection • Experimental challenge in mice • Conserved nucleoprotein and matrix from H1N1 strain (plasmid) in mice, challenge by H5N1 • In pigs – priming with DNA vaccine, boosting with killed virus