Both Neutralizing and Non-Neutralizing Human H7N9 Influenza Vaccine-Induced Monoclonal Antibodies Confer Protection.
Both Neutralizing and Non-Neutralizing Human H7N9 Influenza Vaccine-Induced Monoclonal Antibodies Confer Protection.
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中和和非中和人类H7N9流感疫苗诱导的单克隆抗体提供保护。
DOI：
10.1016/j.chom.2016.05.014
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发表时间：
2016-06-08
影响因子：
30.3
通讯作者：
Wilson PC
中科院分区：
文献类型：
--
作者：
Henry Dunand CJ;Leon PE;Huang M;Choi A;Chromikova V;Ho IY;Tan GS;Cruz J;Hirsh A;Zheng NY;Mullarkey CE;Ennis FA;Terajima M;Treanor JJ;Topham DJ;Subbarao K;Palese P;Krammer F;Wilson PC
致病性 H7N9 禽流感病毒仍然是一个公共卫生问题，目前正在开发几种候选疫苗。评估疫苗接种后是否诱导保护性抗体以及表征目标表位的多样性至关重要。在这里，我们表征了候选 A/Anhui/1/2013 (H7N9) 疫苗诱导的 12 种 H7 反应性人类抗体的结合和功能特性。在被动转移挑战实验中，中和抗体和非中和抗体都能在体内保护小鼠。通过生成针对中和抗体的逃逸突变体变体来绘制 H7 血凝素抗原位点，识别出头部和茎结构域上的独特表位。此外，本研究中产生的广泛交叉反应的非中和抗体通过 Fc 介导的效应细胞募集具有保护作用。这些发现揭示了疫苗诱导抗体的重要特性，并提供了对疫苗背景下人类单克隆抗体对流感的反应的更好理解。
Pathogenic H7N9 avian influenza viruses continue to represent a public health concern and several candidate vaccines are currently being developed. It is vital to assess if protective antibodies are induced following vaccination, and to characterize the diversity of epitopes targeted. Here we characterized the binding and functional properties of twelve H7-reactive human antibodies induced by a candidate A/Anhui/1/2013 (H7N9) vaccine. Both neutralizing and non-neutralizing antibodies protected mice in vivo during passive transfer challenge experiments. Mapping the H7 hemagglutinin antigenic sites by generating escape mutant variants against the neutralizing antibodies identified unique epitopes on the head and stalk domains. Further, the broadly cross-reactive non-neutralizing antibodies generated in this study were protective through Fc-mediated effector cell recruitment. These findings reveal important properties of vaccine-induced antibodies and provide a better understanding of the human monoclonal antibody response to influenza in the context of vaccines.