Structure-function analysis of neutralizing antibodies to H7N9 influenza from naturally infected humans
Structure-function analysis of neutralizing antibodies to H7N9 influenza from naturally infected humans
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DOI：
10.1038/s41564-018-0303-7
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发表时间：
2019-02-01
影响因子：
28.3
通讯作者：
Townsend, Alain R.
中科院分区：
文献类型：
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作者：
Huang, Kuan-Ying A.;Rijal, Pramila;Townsend, Alain R.
关于人类自然H7N9感染诱导的H7反应性抗体库的特异性和中和宽度知之甚少。我们已经从2013年和2014年感染的四名供体的外周B细胞中分离并表征了73种H7反应性单克隆抗体。其中，45种抗体是H7特异性的，其中17种中和了病毒，尽管在其可变结构域序列中几乎没有体细胞突变。从1968年以后出生的年轻供体中分离的另外一组28种抗体在结合测定中在H7和H3血凝素之间发生交叉反应，并且积累了显著更多的体细胞突变，但在体外主要是非中和的。三个中和和保护性抗体的晶体结构与H7血凝素的复合物显示，它们识别血凝素受体结合位点周围的重叠残基。其中一种抗体L4 A-14结合到唾液酸结合位点，并与大多数2016-2017 H7N9分离株中保守的血凝素残基接触。然而，在17种中和抗体中，只有3种保留了对2016-2017年分离的发生抗原性变化的长三角谱系病毒的活性，这强调了更新H7N9疫苗的必要性。
Little is known about the specificities and neutralization breadth of the H7-reactive antibody repertoire induced by natural H7N9 infection in humans. We have isolated and characterized 73 H7-reactive monoclonal antibodies from peripheral B cells from four donors infected in 2013 and 2014. Of these, 45 antibodies were H7-specific, and 17 of these neutralized the virus, albeit with few somatic mutations in their variable domain sequences. An additional set of 28 antibodies, isolated from younger donors born after 1968, cross-reacted between H7 and H3 haemagglutinins in binding assays, and had accumulated significantly more somatic mutations, but were predominantly non-neutralizing in vitro. Crystal structures of three neutralizing and protective antibodies in complex with the H7 haemagglutinin revealed that they recognize overlapping residues surrounding the receptor-binding site of haemagglutinin. One of the antibodies, L4A-14, bound into the sialic acid binding site and made contacts with haemagglutinin residues that were conserved in the great majority of 2016-2017 H7N9 isolates. However, only 3 of the 17 neutralizing antibodies retained activity for the Yangtze River Delta lineage viruses isolated in 2016-2017 that have undergone antigenic change, which emphasizes the need for updated H7N9 vaccines.