Antigenic competition of influenza virus glycoproteins. Immunological and cellular mechanisms responsible for the influence of hemagglutinin priming on the immunogenicity of the viral neuraminidase.
Item
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Title
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Antigenic competition of influenza virus glycoproteins. Immunological and cellular mechanisms responsible for the influence of hemagglutinin priming on the immunogenicity of the viral neuraminidase.
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Identifier
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AAI8914766
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identifier
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8914766
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Creator
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Johansson, Bert Emil.
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Contributor
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Adviser: Edwin D. Kilbourne
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Date
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1988
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Language
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English
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Publisher
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City University of New York.
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Subject
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Health Sciences, Immunology | Biology, Microbiology
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Abstract
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In man, vaccination with neuraminidase (NA) in H7N2 influenza virus antigenic hybrids elicits greater anti-NA response than does N2 NA in H3N2 conventional vaccine, presumably because humans are H3 hemagglutinin (HA) primed and anti-H3 anamnestic response depresses concomitant N2 responses by antigenic competition. BALB/c mice were primed by different schedules of infection with H3N1, H3N2 and H3N7 viruses and given H3N2 and H7N2 vaccines equivalent in NA immunogenicity. In schedules using sequential infections, but not after a single infection with any virus, anti-N2 booster response was four-fold greater with H7N2 vaccine. Thus, HA-influenced suppression of immunologic response to viral NA requires adequate HA priming. Titration of primed helper T (T{dollar}\sb{lcub}\rm h{rcub}{dollar}) cell activity by adoptive transfer of purified T cells to athymic mice and assay of the proliferative response of T cells in B and T cell mixtures stimulated by reassortant influenza viruses in vitro has shown: (1) HA is dominant over NA in both B and T cell priming, (2) an increase in H3 specific B cells occurs in mice boosted with H3N2 vaccine and an increase in N2 specific B cells in those boosted with H7N2 vaccine and, (3) memory B cells function as antigen presenting cells and interact with memory T{dollar}\sb{lcub}\rm h{rcub}{dollar} cells in the mediation of intravirionic HA-NA antigenic competition in favor of HA. Analysis of equivalent macrophage-T cell mixtures demonstrates macrophages from variously immunized and from unimmunized BALB/c mice are equivalent in their capacity as antigen presenting cells when stimulated in vitro with influenza virus.;Immunization of mice with graded doses of purified influenza virus HA and NA antigens demonstrated equivalent responses when HA-specific and NA-specific serum antibodies were measured by enzyme-linked immunosorbent assays (ELISA). Apparently, the antigenic competition between HA and NA glycoproteins results from the difference in their quantitative relationships on the virion surface and not from differences in intrinsic immunogenicity.;Injection of mice with purified H3 HA or N2 NA antigen resulted in immunity manifested by reduction in pulmonary virus following challenge with virus containing homologous antigens. While H3 immunization with all but the lowest doses of antigen prevented infection, immunization with N2 was infection-permissive at all antigen doses. The demonstrable immunogenicity of highly purified neuraminidase as a single glycoprotein without adjuvant and influenced by HA antigenic competition offers a novel approach for human immunization against influenza.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
