Options for Influenza Vaccine Composition Summary of Data Options with Pros and Cons

Influenza A(H1N1) Viruses Little antigenic heterogeneity observed HA of most strains antigenically similar to A/New Caledonia/99 vaccine strain The NA genes of current strains are similar to the vaccine strain Low reactors don’t fall into one genetic group H1N1 viruses are generally well inhibited by ferret and human antiserum vs. A/New Caledonia Current vaccine strain in vaccine for 1 year

H1N1 Option 1: Maintain Current Vaccine Strain Pros –Current vaccine strain is immunogenic and well matched to currently circulating viruses –Manufacturing is well-defined and predictable –No new vaccine candidates are available Con –A variant strain could be identified in the next 2-3 weeks

H1N1 Option 2: Update Current Vaccine Strain Pro –Might provide closer genetic match to next year’s viruses if correct sub lineage is chosen Cons –No clear advantage based on antigenic characterization or serologic results –No superior alternate vaccine candidate

H1N1 Option 3. Defer to Accumulate Additional Data Pro –More data will be available in the next 2-3 weeks (including analyses of new Chinese H1N1 viruses) Con –Additional data may not alter the current considerations since global data consistently indicate a good vaccine match

Summary for Influenza A(H1N1) Viruses Although influenza activity associated with H1N1 viruses has been low worldwide in recent years, significant H1N1 activity has occurred this season. The majority of current viruses are antigenically similar to the A/New Caledonia/99 vaccine strain, however, viruses similar to the A/Johannesburg/96 reference strain were also identified. Human serologic responses suggest that the current vaccine strain is immunogenic and provides a good antibody response against current viruses from both antigenic/genetic groups.

Influenza A(H3N2) Viruses Little antigenic heterogeneity observed HA of most strains antigenically similar to A/Panama/99 vaccine strain The NA genes of many current strains fall into a different genetic group from A/Panama/99 Low reactors (few) do not fall into any particular genetic group H3N2 viruses are generally well inhibited by ferret and human antiserum vs. A/Panama/99 Current vaccine strain in vaccine for 1 year

H3N2 Option 1: Maintain Current Vaccine Strain Pros –Current vaccine strain is immunogenic and well matched to currently circulating viruses –Manufacturing is well-defined and predictable –No obvious new vaccine candidate Con –A new variant might be identified in the next 2- 3 weeks

H3N2 Option 2: Update Current Vaccine Strain Pro –May provide closer genetic match to HA and especially to NA of next year’s viruses Cons –No clear advantage based on antigenic characterization or serologic results –No clear alternate vaccine candidate

H3N2 Option 3: Defer to Accumulate Additional Data Pros –Since H3N2 viruses cause most serious morbidity and mortality, choice should be made carefully –A few additional pieces of data will be available in the next 2-3 weeks Con –Additional data may be insufficient to alter current considerations

Summary for Influenza A(H3N2) Viruses In contrast to most recent years, few H3N2 viruses have been isolated globally. Current viruses are antigenically similar to the A/Panama/99 vaccine strain. Serologic responses suggest that the current vaccine strain is immunogenic and provides an equivalent antibody response against most current viruses.

Influenza B Viruses Antigenic drift has been detected A new variant represented by B/Sichuan/379/99 has been identified as a prototype variant strain The NA genes of many current strains are generally similar to vaccine strain No evidence for circulation of B/Vic-lineage strains B viruses are generally less well inhibited by ferret and human antiserum vs. B/Yamanashi/98 Current vaccine strain in vaccine for 2 years

Influenza B Option 1: Maintain Current Vaccine Strain Pros –Current vaccine strain is immunogenic –Manufacturing is well defined and predictable Cons –Current influenza B strains are not well inhibited by ferret serum to vaccine strain –Human serologic responses vs. recent strains reduced –Egg isolates with appropriate antigenic properties are being evaluated as candidate vaccine strains

Influenza B Option 2: Update Current Vaccine Strain Pros –Provide a better antigenic match with current B strains –Vaccine candidate strains (e.g., B/JHB/5/99 and B/Vic/504/2000) were used to manufacture vaccines for the Southern Hemisphere Cons –No data available on immunogenicity of vaccines produced with recent strains –Many recent influenza B egg isolates grow poorly

Influenza B Option 3: Defer to Accumulate Additional Data Pros –More data will be available in the next 2-3 weeks, including analyses of new Chinese influenza B viruses –More data are likely to be available on growth properties of potential vaccine candidates Cons –Additional data may not alter current considerations

Summary for Influenza B Viruses Antigenic drift from the vaccine strain, B/Yamanashi/98, is apparent among current influenza B viruses which are antigenically and genetically similar to the prototype reference strain, B/Sichuan/379/99. Serologic responses suggest that the current vaccine strain is immunogenic but may provide a more limited response against current B viruses. A great deal of work has been done to develop alternate vaccine candidates.