Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses
Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses
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DOI：
10.1073/pnas.0911806107
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发表时间：
2010-07-13
影响因子：
11.1
通讯作者：
Moyle, Matthew
中科院分区：
文献类型：
--
作者：
Grandea, Andres G., III;Olsen, Ole A.;Moyle, Matthew
流感在全世界仍然是一个严重的公共卫生威胁。疫苗和抗病毒药物可以提供预防感染的保护。然而，由于流感基因组的可塑性，需要每年重新配制疫苗抗原，新的病毒株不断出现，对抗病毒药物的耐药性可能迅速出现，并在流行的病毒种群中根深蒂固。此外，由于设计和制造有效疫苗需要时间，新的大流行毒株的传播难以控制。靶向高度保守的病毒表位的单克隆抗体可能提供另一种保护范例。在这里，我们描述了从健康的人类受试者的IgG（+）记忆B细胞中分离出的一组单克隆抗体，这些单克隆抗体识别流感基质2蛋白M2e的外域内一个以前未知的构象表位。该抗体结合区在甲型流感病毒中高度保守，存在于迄今检测到的几乎所有毒株中，包括主要感染禽类和猪的高致病性病毒，以及目前的2009年猪源H1N1大流行毒株（S-OIV）。此外，这些人抗m2e单克隆抗体可保护小鼠免受H5N1或H1N1流感病毒的致命攻击。这些结果表明，病毒M2e可以在人体内引发广泛的交叉反应性和保护性抗体。因此，这些人抗体的重组形式可能提供有用的治疗剂，以保护免受广谱甲型流感毒株的感染。
Influenza remains a serious public health threat throughout the world. Vaccines and antivirals are available that can provide protection from infection. However, new viral strains emerge continuously because of the plasticity of the influenza genome, which necessitates annual reformulation of vaccine antigens, and resistance to antivirals can appear rapidly and become entrenched in circulating virus populations. In addition, the spread of new pandemic strains is difficult to contain because of the time required to engineer and manufacture effective vaccines. Monoclonal antibodies that target highly conserved viral epitopes might offer an alternative protection paradigm. Herein we describe the isolation of a panel of monoclonal antibodies derived from the IgG(+) memory B cells of healthy, human subjects that recognize a previously unknown conformational epitope within the ectodomain of the influenza matrix 2 protein, M2e. This antibody binding region is highly conserved in influenza A viruses, being present in nearly all strains detected to date, including highly pathogenic viruses that infect primarily birds and swine, and the current 2009 swine-origin H1N1 pandemic strain (S-OIV). Furthermore, these human anti-M2e monoclonal antibodies protect mice from lethal challenges with either H5N1 or H1N1 influenza viruses. These results suggest that viral M2e can elicit broadly cross-reactive and protective antibodies in humans. Accordingly, recombinant forms of these human antibodies may provide useful therapeutic agents to protect against infection from a broad spectrum of influenza A strains.