Antigenic variants of influenza A virus (PR8 strain). V. Virulence, antigenic potency, and cross-protection tests in mice of the original and second series.

Two series of variants of influenza PR8-S virus have been described. While all retain the same degree of pathogenicity for mice and fertile eggs, there was a progressive loss in the ability of the variants to provoke antibody following vaccination or infection of mice and ferrets. The immunogenicity of the variants was, therefore, less than that of the original strain. Although little or no serological relationship could be demonstrated between some of the variants and the PR8-S virus a considerable degree of cross-immunity could be demonstrated in the cross-protection tests with these viruses if observations were based solely on death or survival of the mice. By employing the occurrence of lesions in the lung and the titer of virus in the lung 48 hours after challenge, the amount of cross-protection in mice could be related to the amount of serological cross-reaction. In general mice vaccinated with PR8-S virus were less resistant to infection with the variant viruses than mice vaccinated with variants and challenged with the PR8-S parent virus. The role of the immune environment of the host in the production of the variant influenza viruses with their serological differences, decreasing antigenicity, and persisting pathogenicity as well as the epidemiological implications of these findings with respect to epidemic influenza in man are discussed.