1. Options for Influenza Vaccine Composition 2005-2006 Roland A. Levandowski, M.D. Division of Viral Products Prepared for Vaccines and Related Biological Products Advisory Committee 16-17 February 2005

2. Options for Influenza A H1N1

3. H1N1 Option 1: Retain A/New Caledonia/20/99 PROMOST RECENT H1 VIRUSES ARE A/NEW CALEDONIA/20/99-LIKE BY ANTIGENIC CHARACTERIZATION OF THE HEMAGLUTININ CURRENT VACCINES APPEAR TO BE WELL MATCHED TO HA OF CURRENT STRAINS MANUFACTURING IS WORKED OUT AND YIELD IS PREDICTABLE CONRELATIVELY FEW RECENT STRAINS FOR ANALYSIS

4. H1N1 Option 2: Use a More Recent H1N1 Virus PROA MORE RECENT STRAIN MIGHT PROVIDE A CLOSER MATCH WITH THE HEMAGGLUTININ AND NEURAMINIDASE OF CONTEMPORARY STRAINS CONA NEW STRAIN IS NOT LIKELY TO PROVIDE SUPERIOR IMMUNOGENICITY OR EFFICACY COMPARED TO CURRENT VACCINE STRAIN MANUFACTURING ISSUES FOR NEW STRAINS HAVE NOT BEEN INVESTIGATED

5. H1N1 Option 3: Defer Recommendation PROADDITIONAL ANALYSIS OF CONTEMPORARY STRAINS MIGHT IDENTIFY A CLOSER MATCH FOR THE HEMAGGLUTININ AND NEURAMINIDASE OF NEXT YEAR’S VACCINE CONLITTLE NEW INFORMATION APPEARS FORTHCOMING SINCE H1 VIRUSES ARE CAUSING RELATIVELY LITTLE DISEASE

6. Options for Influenza A H3N2

7. H3N2 Option 1: Retain A/Wyoming/03/2003 PROMANUFACTURING IS WORKED OUT AND YIELD IS PREDICTABLE CONTHE HA OF MOST H3N2 VIRUSES ARE ANTIGENICALLY DISTINGUISHABLE FROM THE CURRENT VACCINE STRAIN SEROLOGICAL RESULTS WITH CURRENT VACCINES INDICATE THAT THE MAJORITY OF STRAINS ARE POORLY INHIBITED BY ANTISERA FROM PEOPLE IMMUNIZED WITH THE CURRENT VACCINES CONTAINING A/WYOMING/03/2003 H3N2 INFLUENZA VIRUSES ARE OFTEN RESPONSIBLE FOR SIGNIFICANT MORBIDITY AND MORTALITY

8. H3N2 Option 2: Use a More Recent H3N2 Virus PROA MORE RECENT STRAIN IS LIKELY TO PROVIDE A CLOSER MATCH WITH CONTEMPORARY STRAINS SEROLOGICAL RESULTS WITH CURRENT VACCINES INDICATES THAT THE MAJORITY OF STRAINS ARE POORLY INHIBITED BY ANTISERA FROM VACCINES CONTAINING A/WYOMING/03/2003 H3N2 INFLUENZA VIRUSES OFTEN CAUSE SIGNIFICANT MORBIDITY AND MORTALITY CONHIGH GROWTH REASSORTANTS FOR A/CALIFORNIA/7/2004-LIKE VIRUSES ARE NOT AVAILABLE, AND YIELD POTENTIAL IS UNDEFINED AT PRESENT

9. H3N2 Option 3: Defer Recommendation PROA MORE RECENT STRAIN IS LIKELY TO PROVIDE A CLOSER MATCH WITH THE HEMAGGLUTININ AND NEURAMINIDASE OF CONTEMPORARY STRAINS H3N2 INFLUENZA VIRUSES OFTEN CAUSE SIGNIFICANT MORBIDITY AND MORTALITY CONA GREAT DEAL OF DATA IS ALREADY AVAILABLE ABOUT H3N2 VIRUSES CURRENTLY CIRCULATING. THESE DATA ARE NOT EXPECTED TO BE SIGNIFICANTLY ENHANCED BY IN THE NEXT FEW WEEKS

10. Options for Influenza B

11. B Option 1: Retain B/Shanghai/361/2002-like Viruses PROMANUFACTURING IS WELL DEFINED AND PREDICTABLE THE PREDOMINANT STRAINS ARE IN THE SAME HA LINEAGE AND HAVE BEEN FOUND IN MANY PARTS OF THE WORLD CONINFLUENZA B VIRUSES NOT IN THE VACCINE HA LINEAGE HAVE INCREASED IN FREQUENCY AND ARE NOT WELL INHIBITED BY POST-INFECTION AND POST-IMMUNIZATION ANTISERA, IN PARTICULAR SERA FROM IMMUNOGLICALLY NAÏVE YOUNG CHILDREN

12. B Option 2: Use a More Recent B Virus PROVACCINES MIGHT PROVIDE BETTER COVERAGE FOR INFLUENZA B VIRUSES CONA NEW STRAIN MAY NOT PROVIDE SUPERIOR IMMUNOGENICITY AND EFFICACY COMPARED TO CURRENT VACCINE STRAIN IT IS NOT CLEAR THAT THE NON-VACCINE STRAINS WILL INCREASE IN FREQUENCY AND ARE NOT FOUND IN ALL AREAS OF THE WORLD NEW INFLUENZA B STRAINS MAY CAUSE DIFFICULTIES IN MANUFACTURING

13. B Option 3: Defer Recommendation PROA MORE RECENT STRAIN MIGHT PROVIDE A CLOSER MATCH WITH THE HEMAGGLUTININ AND NEURAMINIDASE OF CONTEMPORARY STRAINS CONA NEW STRAIN MAY NOT PROVIDE SUPERIOR IMMUNOGENICITY AND EFFICACY COMPARED TO CURRENT VACCINE STRAIN ADDITIONAL SIGNIFICANT INFORMATION IS NOT LIKELY TO BE FORTHCOMING

14. Question for Committee Recommendation What strains should be recommended for the antigenic composition of the 2005-2006 influenza virus vaccine? Based on Epidemiology and antigenic characteristics Serologic Responses Availability of candidate strains