Antigenic variants of influenza A virus obtained in vitro

The aim of this study was to investigate antigenic "drift" in the haemagglutinin and neuraminidase antigens of influenza A virus in vitro under immunological pressure. Variants of the "Asian" influenza strains A/England/12/64 (H2N2) and A/Tokyo/3/67 (H2N2) were isolated in the allantois-on-shell system in the presence of homologous postinfection ferret sera. For each of these two viruses three generations of variants were isolated and characterized. It was found that the successive antigenic variants of A/Eng/12/64 did not resemble A/Tokyo/3/67. Thus it is probable that the pathway of antigenic drift in vitro was not the same as that which occurred in nature during the evolution of A/Tokyo/3/67 from A/Eng/12/64. In addition, A/Tokyo/3/67, which was the last strain to be prevalent before the A/Hong Kong subtype appeared, underwent significant antigenic drift from "junior" to "senior" variants. This finding did not support the concept that, when antigenic drift occurs, resulting in the appearence of viruses with new haemagglutinin antigen subtypes, the previously prevalent strain has no capacity for further antigenic drift. The study did not result in the production of strains that were identifiable as "bridging" viruses between the H2 and H3 haemagglutinin subtypes. The present paper includes the first report of antigenic variation in the neuraminidase antigens of influenza A viruses occurring in vitro under immunological pressure.