Antigenic Variants of Influenza a Virus (pr8 Strain) I I I . Serological Relationships of a Line of Variants Derived in Sequence in Mice given Homologous

During the past three years experimental studies to determine the role of the immune state of the host (the mouse) in the development of antigenic variants of influenza virus type A have been made. At the present time, seven successive generations of antigenic variants of influenza A PR8-S virus, each derived from the previous one by serial passage in the lungs of mice immunized with the homologous agent, have been produced. These variants show no change when passed in non-immune animals. The details of the methods employed, the serological and immunological characteristics of the first four variants compared with the parent PR8-S strain have been published (1, 2). As previously reported the first four variants showed a progressive serological deviation from the parent PR8-S virus. However, while showing progressively less ability to react with antisera of the preceding variants and the PR8-S virus they retained the capacity to provoke antibody to the preceding variants and the parent virus (2). The three most recently derived variants show essentially no reaction with PR8 antiserum while continuing to elicit considerable amounts of antibody which react with the preceding variants and the original PR8-S virus. This report gives (a) the serological relationships of the seven variants to one another and to the original parent PR8 virus and (b) the results of cross-hemagglutinin inhibition tests with the certain epidemic A and A' strains and the variant viruses.