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Antibodies to the Strain‐Specific and Cross‐Reactive Determinants of the Haemagglutinin of Influenza H3N2 Viruses

The serological analysis of antibodies to the haemagglutinin (HA) of influenza A viruses of the Hong Kong (H3N2) subtype is described, using haemagglutination‐inhibition, immuno‐double‐diffusion and single‐radial‐diffusion techniques. By cross‐absorption of antisera to purified HA antigens, different populations of antibody molecules were obtained, which are designated strain‐specific and cross‐reactive and characterized in terms of their antigenic specificities for HA antigens of the homologous and antigenically variant H3N2 viruses. A narrowly strain‐specific population of antibodies (SS“HK) was obtained as the residual antibody in antiserum to A/Hong Kong/1/68 HA after absorption with the closely related A/England/42/72 virus, whilst a contrasting broadly cross‐reactive population (CR‘HK) was obtained by absorption of the anti‐A/Hong Kong/1/68 HA serum with the more distantly related strain A/Victoria/3/75 and eluting the cross‐reactive antibodies from the absorbing virus. Similarly, specific and cross‐reactive antibodies were derived from antiserum to A/Victoria/3/75 HA antigen by absorption with A/Hong Kong/1/68 virus. Single‐radial‐diffusion tests were performed, involving sequential application of different antibody preparations in the same wells in immunoplates containing intact virus particles. The cross‐reactive and strain‐specific antibodies differed in their property of mutual interference of attachment to antigen. The results suggested that the cross‐reactive antigenic determinants on the HA subunit may be located closer to the distal end of the molecule than the strain‐specific determinants. Further tests employing single‐radial‐diffusion showed that there are more cross‐reactive than strain‐specific sites available for antibody in the intact virus particle. The strain‐specific antibodies also gave higher haemagglutination‐inhibition titres per ***μg IgG than the cross‐reactive antibodies.