Immunization with purified N1 and N2 influenza virus neuraminidases demonstrates cross-reactivity without antigenic competition.

Based on the absence of serologic cross-reactivity, the neuraminidases (NAs) of influenza A viruses are divided into antigenically discrete subtypes, analogous to the hemagglutinin (HA) major antigens with which they share the virion surface. An innovative approach to influenza vaccination takes advantage of the infection-permissive nature of immunization with NA as the minor surface antigen. However, evidence that HA dominates immune response when HA and NA are presented together in the intact virion prompted investigation of possible competing effects during immunization of NA subtype mixtures ultimately required for human vaccination. Immunization of BALB/c mice with purified N1- and N2-subtype NAs demonstrated no antigenic competition in primary or secondary response. However, when homotypic or heterotypic infection followed immunization, cross-reactive antibodies between N1 and N2 were found and "reverse antigen competition" occurred with initial NA priming suppressing response to HA following infection with virus containing homologous NA. These studies of antigen mixtures have implications for the use of combined and chimeric vaccines for diseases other than influenza.