Immunogenicity of a contiguous T-B synthetic epitope of the A/PR/8/34 influenza virus.
A contiguously linked T-B synthetic viral epitope (110HA120-150HA159,T-B) was investigated for its potency in inducing humoral and cellular immune responses in vivo. The T-cell epitope 110HA120 corresponds to the site 1 hemagglutinin (HA) of the A/PR/8/34 (PR8) influenza virus and is recognized by CD4 T cells in association with I-Ed class II major histocompatibility complex molecules. The 150HA159 represents a major B-cell epitope of the HA protein. T-B dipeptide emulsified in Freund's complete adjuvant was able to induce strong antiviral antibody titers and a high frequency of specific T-cell precursors after a single inoculation in BALB/c mice. In contrast, immunization under identical conditions with equimolar mixtures of T and B peptides did not elicit antibody titers or a cellular immune response. As indicated by the isotypes of antiviral antibodies, the T-B dipeptide preferentially induced a Th1-like immune response. Challenge with T-B dipeptide, but not with T or B peptide alone, stimulated peptide-specific T memory cells in mice previously primed with PR8 virus or with T-B dipeptide. As a consequence, 71 and 57% of these mice, respectively, survived infection with two 100% lethal doses of PR8 virus. Our results suggest that, inasmuch as contiguity between T- and B-cell epitopes provides enough signaling capacity to trigger the mechanisms of T-B-cell cooperation in vivo, a T-B contiguous epitope may well represent a minimal built-in subunit vaccine. Aside from their potential bioavailability, the T-B contiguous epitopes may also represent attractive tools for investigating the molecular mechanisms of T-B-cell cooperation responsible for antiviral protection.
Brumeanu
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Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Casares
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D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D007125:Immunogenetics; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D014614:Vaccines, Synthetic / Q000276:immunology*
D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D014614:Vaccines, Synthetic