Immunization with dissociated neuraminidase, matrix, and nucleoproteins from influenza A virus eliminates cognate help and antigenic competition.

When hemagglutinin (HA) and neuraminidase (NA) are presented together on an intact influenza virus particle, the antigens are competitive, with HA dominant over NA in T- and B-cell priming. Immunization with mixtures of purified HA and NA eliminates antigenic competition between HA and NA, as well as between N1-N2 NA mixtures. Evidence that vaccine preparations contain influenza virus matrix (M1) and nucleoprotein (NP) prompted the investigation of possible competing effects of these proteins on the anti-HA and anti-NA immune response. However, in BALB/c mice immunized with mixtures of purified NA, M1, and NP no antigenic competition was demonstrated in either the primary or the secondary response. When mice were immunized with intact virus or by infection, a lesser antibody response to M1 and NP was observed. Furthermore, as measured by mean pulmonary virus titers after infection, no additional protective effects were conferred on mice immunized with M1 and NP either alone or in conjunction with other antigens. These studies of influenza virus antigen mixtures have implications for vaccination against influenza and other vaccines consisting of combinations of antigens.