Preparation and immunogenicity of an influenza virus hemagglutinin and neuraminidase subunit vaccine

Abstract

Vaccines containing hemagglutinin and neuraminidase subunits were prepared from the A/Port Chalmers/1/73 (H3N2) strain of influenza virus. The virus particles were disrupted with ammonium deoxycholate and the matrix protein, which was insoluble in this detergent, was removed by centrifugation. Following removal of deoxycholate, the hemagglutinin and neuraminidase subunits aggregated by their hydrophobic ends, forming mixed clusters. These were then freed from nucleocapsids by electrophoresis. The separated nucleocapsid protein and the matrix protein were thus obtained as byproducts in a highly purified form suitable for the production of antisera and for structural studies. The hemagglutinin and neuraminidase subunits were as effective as intact inactivated virus (at equivalent concentration) in eliciting a late primary antibody response when injected in saline into rabbits. In hamsters, the subunits failed to induce antibody when injected in saline (in contrast to intact virus), but the immune response to the subunits could be potentiated by the simultaneous injection of an intact heterologous influenza A or B virus.