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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Vaccination with a synthetic peptide from the influenza virus hemagglutinin provides protection against distinct viral subtypes
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Vaccination with a synthetic peptide from the influenza virus hemagglutinin provides protection against distinct viral subtypes

机译：用流感病毒血凝素合成肽进行疫苗接种可提供针对不同病毒亚型的保护

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摘要

Current influenza virus vaccines protect mostly against homologous virus strains; thus, regular immunization with updated vaccine formulations is necessary to guard against the virus' hallmark remodeling of regions that mediate neutralization. Development of a broadly protective influenza vaccine would mark a significant advance in human infectious diseases research. Antibodies with broad neutralizing activity (nAbs) against multiple influenza virus strains or subtypes have been reported to bind the stalk of the viral hemagglutinin, suggesting that a vaccine based on this region could elicit a broadly protective immune response. Here we describe a hemagglutinin subunit 2 protein (HA2)-based synthetic peptide vaccine that provides protection in mice against influenza viruses of the structurally divergent subtypes H3N2, H1N1, and H5N1. The immunogen is based on the binding site of the recently described nAb 12D1, which neutralizes H3 subtype viruses, demonstrates pro tective activity in vivo, and, in contrast to a majority of described nAbs, appears to bind to residues within a single a-helical portion of the HA2 protein. Our data further demonstrate that the specific de sign of our immunogen is integral in the induction of broadly active anti-hemagglutinin antibodies. These results provide proof of con cept for an HA2-based influenza vaccine that could diminish the threat of pandemic influenza disease and generally reduce the sig nificance of influenza viruses as human pathogens.
机译：当前的流行性感冒病毒疫苗大多能抵抗同源病毒株。因此，必须定期使用更新的疫苗制剂进行免疫，以防止介导中和区域的病毒标志性重塑。广泛保护性流感疫苗的开发将标志着人类传染病研究的重大进展。据报道，针对多种流感病毒株或亚型具有广泛中和活性的抗体可结合病毒血凝素的茎，这表明基于该区域的疫苗可引起广泛的保护性免疫应答。在这里，我们描述了一种基于血凝素亚基2蛋白（HA2）的合成肽疫苗，该疫苗在小鼠中提供针对结构上不同的H3N2，H1N1和H5N1亚型流感病毒的保护。免疫原基于最近描述的nAb 12D1的结合位点，该结合位点可中和H3亚型病毒，在体内具有保护作用，并且与大多数描述的nAb相比，似乎与单个a螺旋内的残基结合HA2蛋白的一部分。我们的数据进一步证明，我们免疫原的特异性设计在诱导广泛活性的抗血凝素抗体中不可或缺。这些结果提供了基于HA2的流感疫苗概念的证据，该疫苗可以减少大流行性流感疾病的威胁并通常降低流感病毒作为人类病原体的重要性。

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    Taia T. Wang; Gene S. Tan; Rong Hai; Natalie Pica; Lily Ngai; Damian C. Ekiert; Ian A. Wilson; Adolfo Garcia-Sastre; Thomas M. Moran; Peter Palese;

  • 作者单位

    Departments of Microbiology Mount Sinai School of Medicine, New York, NY 10029;

    rnDepartments of Microbiology Mount Sinai School of Medicine, New York, NY 10029;

    rnDepartments of Microbiology Mount Sinai School of Medicine, New York, NY 10029;

    rnDepartments of Microbiology Mount Sinai School of Medicine, New York, NY 10029;

    rnDepartments of Microbiology Mount Sinai School of Medicine, New York, NY 10029;

    rnDepartment of Molecular Biology The Scripps Research Institute, La Jolla, CA 92037;

    rnDepartment of Molecular Biology The Scripps Research Institute, La Jolla, CA 92037 Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037;

    rnDepartments of Microbiology Mount Sinai School of Medicine, New York, NY 10029 Departments of Medicine, Mount Sinai School of Medicine, New York, NY 10029 Departments of Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, NY 10029;

    rnDepartments of Microbiology Mount Sinai School of Medicine, New York, NY 10029 Departments of Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029;

    rnDepartments of Microbiology Mount Sinai School of Medicine, New York, NY 10029 Departments of Medicine, Mount Sinai School of Medicine, New York, NY 10029;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    mice; pandemic; synthetic peptide; vaccine; HA2;

    机译：老鼠;大流行;合成肽疫苗;HA2;

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