Scientific Publications by FDA Staff

Influenza Other Respir Viruses 2012 May;6(3):176-87

Determination of H5N1 vaccine potency using reference antisera from heterologous strains of influenza.

Vodeiko GM, Weir JP

Background Standardization of inactivated influenza vaccines by hemagglutinin (HA) content is performed by the single radial immunodiffusion (SRID) method. Regulatory agencies prepare, calibrate, and distribute SRID reagent standards necessary for testing of seasonal influenza vaccines, and a similar process is used to produce potency reagents for candidate pandemic influenza vaccines that are manufactured for emergency stockpiles. Objectives Because of the concerns in generating a timely strain-specific potency antiserum for an emerging pandemic virus, we evaluated the feasibility of using heterologous potency reference antiserum as a replacement for a strain-specific (homologous) antiserum in the SRID potency assay for stockpiled H5N1 vaccines. Results The results indicate that a heterologous H5N1 antiserum can be used to determine the accurate potency of inactivated H5N1 influenza vaccines. Additionally, when H5N1 vaccine was subjected to an accelerated stability protocol, both homologous and heterologous antisera provided similar measurements of vaccine potency decline. Limitations to the heterologous antiserum approach to potency determination were shown by the inability of antiserum to recent seasonal H1N1 viruses to work in an SRID assay with the 2009 pandemic H1N1 A/California/07/2009 antigen. Conclusions The data demonstrate the feasibility of using heterologous antiserum for potency determination of at least some candidate vaccines in case of a shortage or delay of homologous antiserum. Further, the results suggest the prudence of stockpiling a broad library of potency reagents including many strains of influenza viruses with pandemic potential to provide an added measure of assurance that reagent production would not be a bottleneck to vaccine production during a pandemic.