Immunization with influenza A virus hemagglutinin and neuraminidase produced in recombinant baculovirus results in a balanced and broadened immune response superior to conventional vaccine

Abstract

Influenza A virus hemagglutinin (HA) and neuraminidase (NA) from A/Nanchang/933/95 were expressed by recombinant baculovirus-infected insect cell lines. HA and NA were chromatographically purified then combined in a single vaccine preparation. Immunization of mice with this preparation resulted in high titers of antibodies to both HA and NA equivalent for each antigen to titers in animals immunized with either antigen alone. Anti-NA antibody titers, measured by either enzyme linked immunoabsorbant assay or neuraminidase inhibition test were higher in the combined recombinant vaccine than in conventional monovalent inactivated vaccine. There was no difference in the anti-HA antibody titers between these two vaccine preparations. Homotypic and closely related heterotypic infections were suppressed and greater reduction in viral replication was observed following a distantly related heterotypic infectious challenge than was observed with conventional inactivated vaccine. The combined HA and NA vaccine takes advantage of the equivalent immunogenicity of dissociated HA and NA, to produce a broader and more balanced immune response to both antigens, without the HA-dominant antigenic competition that occurs with natural infection or immunization with conventional vaccine. Additionally, the recombinant baculovirus expression system offers a reliable rapid production system without the use of massive numbers of embryonated chicken eggs. These studies in a mouse model system suggest that production of a combined HA and NA vaccine from recombinant baculovirus offers an improved alternative to conventional inactivated influenza vaccine.