Hemagglutinin stalk antibodies elicited by the 2009 pandemic influenza virus as a mechanism for the extinction of seasonal H1N1 viruses
Hemagglutinin stalk antibodies elicited by the 2009 pandemic influenza virus as a mechanism for the extinction of seasonal H1N1 viruses
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DOI：
10.1073/pnas.1200039109
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发表时间：
2012-02-14
影响因子：
11.1
通讯作者：
Palese, Peter
中科院分区：
文献类型：
--
作者：
Pica, Natalie;Hai, Rong;Palese, Peter
在1957年、1968年和2009年出现大流行性流感病毒后，观察到人群中现有的季节性病毒被新的大流行毒株所取代。我们先前假设，季节性菌株的替换部分是由血凝素柄和病毒神经氨酸酶保守区域特异性抗体的群体规模增强介导的。最近的许多研究表明，茎特异性抗体在中和流感病毒中的作用；茎抗体可以有效中和病毒的发现改变了现有的教条，即流感病毒中和仅仅是由与病毒血凝素球形头反应的抗体介导的。目前的研究探索了一种可能性，即感染2009年H1N1大流行病毒后，茎特异性抗体增强，这些抗体可能导致现有的季节性H1N1流感病毒株消失。为了研究茎特异性抗体，我们开发了嵌合血凝素结构，可以测量结合血凝素蛋白和中和病毒但不具有血凝抑制活性的抗体。使用这些嵌合血凝素试剂，我们发现感染2009年H1N1大流行病毒引起了针对血凝素柄的病毒中和抗体滴度的提高。此外，我们描述了可用于测量流感病毒中和抗体的测定，这些抗体在传统的血凝抑制测定中未被检测到。
After the emergence of pandemic influenza viruses in 1957, 1968, and 2009, existing seasonal viruses were observed to be replaced in the human population by the novel pandemic strains. We have previously hypothesized that the replacement of seasonal strains was mediated, in part, by a population-scale boost in antibodies specific for conserved regions of the hemagglutinin stalk and the viral neuraminidase. Numerous recent studies have shown the role of stalk-specific antibodies in neutralization of influenza viruses; the finding that stalk antibodies can effectively neutralize virus alters the existing dogma that influenza virus neutralization is mediated solely by antibodies that react with the globular head of the viral hemagglutinin. The present study explores the possibility that stalk-specific antibodies were boosted by infection with the 2009 H1N1 pandemic virus and that those antibodies could have contributed to the disappearance of existing seasonal H1N1 influenza virus strains. To study stalk-specific antibodies, we have developed chimeric hemagglutinin constructs that enable the measurement of antibodies that bind the hemagglutinin protein and neutralize virus but do not have hemagglutination inhibition activity. Using these chimeric hemagglutinin reagents, we show that infection with the 2009 pandemic H1N1 virus elicited a boost in titer of virus-neutralizing antibodies directed against the hemagglutinin stalk. In addition, we describe assays that can be used to measure influenza virus-neutralizing antibodies that are not detected in the traditional hemagglutination inhibition assay.