Vaccination with a synthetic peptide from the influenza virus hemagglutinin provides protection against distinct viral subtypes
Vaccination with a synthetic peptide from the influenza virus hemagglutinin provides protection against distinct viral subtypes
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DOI：
10.1073/pnas.1013387107
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发表时间：
2010-11-02
影响因子：
11.1
通讯作者：
Palese, Peter
中科院分区：
文献类型：
--
作者：
Wang, Taia T.;Tan, Gene S.;Palese, Peter
目前的流感病毒疫苗主要针对同源病毒株提供保护;因此，有必要使用更新的疫苗制剂进行定期免疫接种，以防止病毒对介导中和的区域进行标志性重塑。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的具有广泛中和活性（nAb）的抗体结合病毒血凝素的茎，这表明基于该区域的疫苗可以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单位2蛋白（HA 2）的合成肽疫苗，该疫苗在小鼠中提供针对结构上不同的亚型H3 N2、H1N1和H5 N1流感病毒的保护。该免疫原基于最近描述的nAb 12 D1的结合位点，其中和H3亚型病毒，在体内显示保护活性，并且与大多数描述的nAb相反，似乎与HA 2蛋白的单个α-螺旋部分内的残基结合。我们的数据进一步表明，我们的免疫原的特定设计是诱导广泛活性的抗血凝素抗体的组成部分。这些结果为基于HA 2的流感疫苗提供了概念证明，该疫苗可以减少大流行性流感疾病的威胁，并普遍降低流感病毒作为人类病原体的重要性。
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 protective 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 design of our immunogen is integral in the induction of broadly active anti-hemagglutinin antibodies. These results provide proof of concept for an HA2-based influenza vaccine that could diminish the threat of pandemic influenza disease and generally reduce the significance of influenza viruses as human pathogens.