ANTIGENIC VARIANTS OF INFLUENZA A VIRUS (PR8 STRAIN)

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Abstract
Four generations of antigenic variants of influenza PR 8 virus each derived in succession from the previous one by serial passage in the lungs of mice immunized with the homologous agent were compared with the original parent PR 8 virus with respect to their serological and immunological character. It was demonstrated by means of hemagglutinin-inhibition, complement fixation and in ovo neutralization tests that the variants exhibited a progressively decreasing reactivity with the parent PR 8 antiserum while retaining the ability to elicit antibody to PR 8 influenza virus and to their respective predecessors. Accompanying these changes was a reduction in antigenicity without any significant changes in pathogenicity for mice. Experimental evidence was presented which indicated that the serological changes observed with the variants are not related to the P-Q phenomenon. Mice vaccinated with PR 8 vaccine were protected against fatal infection with lethal doses of the variant strain although the latter had a progressively decreasing reactivity with PR 8 antiserum. The inheritable character of the new antigenic properties of the variant strains was demonstrated by their persistence in the absence of the selective environment following 18 to 24 serial intranasal passages in normal mice and following limiting dilution passages in fertile eggs.