Immune response of human volunteers and animals to vaccination with egg-grown influenza A (H1N1) virus is influenced by three amino acid substitutions in the haemagglutinin molecule

Inactivated subunit vaccines were prepared from high-growth reassortants derived from two separate egg isolates from a single clinical specimen of influenza A (H1N1) virus. One of these reassortants, NIB-14, was antigenically indistinguishable from isolates made in tissue culture, while the other, NIB-17, was antigenically different and typical of egg isolates. The viruses differed by three amino acid residues in the haemagglutinin (HA) molecule and the anti-HA serological response induced was studied in animal models and human volunteers. In the volunteer groups both vaccines induced very high levels of circulating haemagglutination inhibition antibodies but with different serological specificities. Both NIB-14 and NIB-17 vaccines induced high levels of cross-reactive antibodies capable of reacting with both strains, but only NIB-14 vaccine induced significant levels of strain-specific antibodies capable of reacting exclusively with the homologous strain. Antisera containing only cross-reactive antibodies proved as capable of virus neutralization as antisera containing high levels of strain-specific antibodies. We extended the argument that epidemic strains are antigenically more closely related to tissue culture isolates and established that viruses which differ by only single amino acids at critical points in the HA structure can induce a significantly different immune response when used as inactivated vaccines.