Nonimmunoselected intrastrain genetic variation detected in pairs of high-yielding influenza A (H3N2) vaccine and parental viruses.

Seven influenza A (H3N2) high-yielding vaccine candidate strains were examined. Antigenic analysis revealed that 5 of the strains could be distinguished antigenically from their corresponding wild type parent viruses. Comparative sequence data for the HA1 domains of the HA (hemagglutinin) genes for these 5 high-yielding viruses and the corresponding wild type parents demonstrated one to three amino acid substitutions within each virus pair, with at least one amino acid change being located in a previously defined antigenic site. Comparison of the HA sequences of the 2 antigenically indistinguishable virus pairs revealed no amino acid differences in 1 and one amino acid change in the other. Examination of 1 additional wild type virus, A/Guangdong/39/89, and its three high-yielding derivatives obtained either by serial egg passage or by reassortment revealed an additive effect of the HA and M genes in creating the high-yielding phenotype.