Biomedical subjects
Publications and source records attributed to P GERBER.
Algal polysaccharide obtained from carrageenin protects 80 to 100 percent of chicken embryos against fatal infections with the Lee strain of influenza virus. This report describes the rapid emergence of a stable variant of this virus which is resistant to the protective action of this polysaccharide.
Seven variant strains 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. With the H.I. and neutralization procedures these variants showed a progressive serological deviation from the parent PR8-S virus. The seven variants provoked antibodies in varying titers to the preceding variants and the parent virus but not in relation to their position in the series. Thus, the seventh variant provoked significantly more antibody to the PR8-S virus than did the fifth variant. A possible explanation for this is presented. The first four variant viruses showed progressively less ability to react with antisera of the preceding variants and the PR8-S virus, and the three most recently derived variants showed essentially no ability to react with PR8-S and first variant antisera. The variant viruses remained antigenically stable through numerous lung passages in normal mice. Cross absorption tests revealed common antigenic components among the variant viruses and also individual characteristics which classify them as being different from one another. The implications of these findings in relation to studies by others have been discussed.
A second series of four variants of PR8-S virus has been produced by passage of the variants in the lungs of mice immunized with the PR8-S virus as well as the homologous strain. The PR8-S virus was added as a constant component of the vaccine so that a high antibody titer to it would suppress selectively the development of variants with PR8-S characteristics. Comparative H.I. and in ovo neutralization tests with the first and second series of variants revealed that the three variants, Fd/s, Gf/s, and Hg/s, of the second series, failed to react with PR8-S antisera and produced significantly smaller amounts of antibody which reacted with PR8-S, the variants of the first series, and the first variant (D/s) of the second series. Although these three variants reacted quite similarly in the H.I. and neutralization tests cross-absorption of these sera with the PR8-S virus and themselves revealed individual antigenic characteristics. While these studies emphasize the importance of the immune state of the host the precise mechanism in the selection of a new antigenic component in the emerging variant must yet be determined.
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.
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Four successive generations of antigenic variants of influenza PR8-S virus, each derived from the previous one by serial passage in the lungs of mice immunized with the homologous agent, were compared with the original parent PR8-S virus with respect to their serological and immunological character. It was demonstrated by means of H.I., complement-fixation and in ovo-neutralization tests that the variants exhibited a progressively decreasing reactivity with the parent PR8-S antiserum while retaining the ability to elicit antibody to PR8-S influenza virus and to their respective predecessors. Accompanying these changes was a progressive reduction in antigenicity without any significant changes in pathogenicity for mice. Experimental evidence was presented which indicates that the serological changes observed with the variants are not related to the P-Q phenomenon. Antibody absorption tests showed that the variants share antigens with PR8-S virus but differ from it by the presence of specific antigenic components; these increase in quantity with each successive variant while the amount of related antigens shows a progressive decrease. The importance of evaluating the significance of antigenic changes of influenza viruses with active immunity tests was emphasized by the fact that PR8-S vaccine protected mice against fatal infection with lethal doses of the variant strains although the latter had a progressively decreasing serological reactivity with PR8-S antiserum. The inheritable character of the new antigenic properties of the variant strains was demonstrated by their persistence in the absence of thea selective environment following 18 to 24 serial intranasal passages with large inocula in normal mice and following limiting dilution passage in fertile eggs.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.