Immunologic response to influenza virus neuraminidase is influenced by prior experience with the associated viral hemagglutinin: II. Sequential infection of mice simulates human experience

In man, vaccination with neuraminidase (NA) in H7N2 virus hybrids elicits greater anti-NA response than does N2 NA in H3N2 conventional vaccine, presumably because humans are H3 hemagglutinin (HA) primed and anti-H3 anamnestic response depresses concomitant N2 responses by antigenic competition. In a laboratory model, BALB/c mice were primed by different schedules of infection with H3N1, H3N2, and H3N7 viruses and given H3N2 and H7N2 vaccines equivalent in NA immunogenicity. In schedules using sequential infections, but not after a single infection with any virus, anti-N2 booster response was fourfold greater with H7N2 vaccine and was reciprocal to the magnitude of anti-H3 response. Thus, HA-influenced suppression of immunologic response to viral NA requires adequate HA priming but is not unique to man and can be studied in the murine model. An incidental finding of this study was the sharing of cross-reactive determinants by N1, N2, and N7 NA.