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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells
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Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells

机译：大流行H1N1流感疫苗在人体内引起召回反应，有利于广泛的交叉反应性记忆B细胞

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摘要

We have previously shown that broadly neutralizing antibodies reactive to the conserved stem region of the influenza virus hemag-glutinin (HA) were generated in people infected with the 2009 pandemic H1N1 strain. Such antibodies are rarely seen in humans following infection or vaccination with seasonal influenza virus strains. However, the important question remained whether the inactivated 2009 pandemic H1N1 vaccine, like the infection, could also induce these broadly neutralizing antibodies. To address this question, we analyzed B-cell responses in 24 healthy adults immunized with the pandemic vaccine in 2009. In all cases, we found a rapid, predominantly IgG-producing vaccine-specific plasmablast response. Strikingly, the majority (25 of 28) of HA-specific monoclonal antibodies generated from the vaccine-specific plasmablasts neutralized more than one influenza strain and exhibited high levels of somatic hypermutation, suggesting they were derived from recall of B-cell memory. Indeed, memory B ceils that recognized the 2009 pandemic H1N1 HA were detectable before vaccination not only in this cohort but also in samples obtained before the emergence of the pandemic strain. Three antibodies demonstrated extremely broad cross-reactivity and were found to bind the HA stem. Furthermore, one stem-reactive antibody recognized not only H1 and H5, but also H3 influenza viruses. This exceptional cross-reactivity indicates that antibodies capable of neutralizing most influenza subtypes might indeed be elicited by vaccination. The challenge now is to improve upon this result and design influenza vaccines that can elicit these broadly cross-reactive antibodies at sufficiently high levels to provide heterosubtypic protection.
机译：我们以前已经表明，在感染2009年大流行H1N1病毒的人群中会产生与流感病毒血凝素（HA）的保守茎区有反应的广泛中和抗体。在季节性流感病毒株感染或接种疫苗后，此类抗体在人类中很少见。但是，重要的问题仍然是，灭活的2009年大流行H1N1疫苗是否像感染一样也可以诱导这些广泛中和的抗体。为了解决这个问题，我们分析了2009年使用大流行疫苗免疫的24位健康成年人的B细胞应答。在所有情况下，我们都发现了快速的，主要是产生IgG的疫苗特异性成浆细胞应答。令人惊讶的是，从疫苗特异性浆母细胞生成的大多数HA特异性单克隆抗体（28种中的25种）中和了一种以上的流感病毒株，并表现出高水平的体细胞超突变，表明它们源自B细胞记忆的回忆。确实，不仅在这一人群中，而且在大流行株出现之前获得的样品中，都可以在疫苗接种之前检测到识别2009年H1N1 HA大流行的记忆B细胞。三种抗体表现出极宽的交叉反应性，并发现与HA茎结合。此外，一种干反应抗体不仅识别H1和H5，而且识别H3流感病毒。这种非凡的交叉反应性表明，疫苗接种确实可以引发能够中和大多数流感亚型的抗体。现在的挑战是改善这一结果并设计流感疫苗，以足够高的水平引发这些广泛的交叉反应抗体，以提供异型保护。

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  • 作者

    Gui-Mei Li; Christopher Chiu; Jens Wrammert; Megan McCausland; Sarah F. Andrews; Nai-Ying Zheng; Jane-Hwei Lee; Min Huang; Xinyan Qu; Srilatha Edupuganti; Mark Mulligan; Suman R. Das; Jonathan W. Yewdell; Aneesh K. Mehta; Patrick C. Wilson; Rafi Ahmed;

  • 作者单位

    Emory Vaccine Center, School of Medicine, Emory University, Atlanta, GA 30322 Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA 30322;

    Emory Vaccine Center, School of Medicine, Emory University, Atlanta, GA 30322 Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA 30322;

    Emory Vaccine Center, School of Medicine, Emory University, Atlanta, GA 30322 Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA 30322;

    Emory Vaccine Center, School of Medicine, Emory University, Atlanta, GA 30322 Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA 30322;

    Department of Medicine, Section of Rheumatology, The Committee on Immunology, The Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637;

    Department of Medicine, Section of Rheumatology, The Committee on Immunology, The Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637;

    Department of Medicine, Section of Rheumatology, The Committee on Immunology, The Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637;

    Department of Medicine, Section of Rheumatology, The Committee on Immunology, The Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637;

    Department of Medicine, Section of Rheumatology, The Committee on Immunology, The Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637;

    Hope Clinic of the Emory Vaccine Center, School of Medicine, Emory University, Atlanta, GA 30322;

    Hope Clinic of the Emory Vaccine Center, School of Medicine, Emory University, Atlanta, GA 30322;

    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892;

    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892;

    Hope Clinic of the Emory Vaccine Center, School of Medicine, Emory University, Atlanta, GA 30322 Division of Infectious Diseases, School of Medicine, Emory University, Atlanta, GA 30322 Department of Internal Medicine, School of Medicine, Emory University, Atlanta, GA 30322;

    Department of Medicine, Section of Rheumatology, The Committee on Immunology, The Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637;

    Emory Vaccine Center, School of Medicine, Emory University, Atlanta, GA 30322 Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA 30322;

  • 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
  • 中图分类
  • 关键词

    immunity; stalk; immunoglobulin; neutralization;

    机译：免疫;茎;免疫球蛋白中和;

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