Immunization against influenza A virus: Comparison of conventional inactivated, live-attenuated and recombinant baculovirus produced purified hemagglutinin and neuraminidase vaccines in a murine model system

To simulate the 2003-2004 influenza season and compare available vaccination methods, immunologically naive mice were immunized with: influenza A virus hemagglutinin (rHA) and neuraminidase (rNA) from A/Panama/2007/99 H3N2 or A/Fujian/411/2002 H3N2 expressed by recombinant baculovirus, chromatographically purified, either as single antigens (rHA or rNA) or in combination (rHArNA); conventional inactivated monovalent (CIV) vaccines from each heterotypic strain; or a live-attenuated influenza (LAV) vaccine derived from the A/Panama/2007/99 strain. HA containing vaccines were highly immunogenic for the HA antigen, with no statistically significant differences among groups in the amount of homotypic anti-HA antibody induced. Little cross-reactive anti-HA antibody was induced by any vaccine, including LAV. Statistically, the greatest amount of anti-NA antibody was induced by the purified NA alone or in combination with purified HA; the least amount of anti-NA antibody was found in mice immunized with LAV or CIV. Immunization with vaccines immunogenic for both HA and NA resulted in an immune response to both surface glycoproteins that suppressed homotypic, closely related heterotypic infection and had a greater reduction in mPVT following an infectious challenge by a distantly related heterotypic strain. These studies suggest that vaccines immunogenic for both HA and NA offer an increased level of protection from influenza.