A potent broad-spectrum protective human monoclonal antibody crosslinking two haemagglutinin monomers of influenza A virus
A potent broad-spectrum protective human monoclonal antibody crosslinking two haemagglutinin monomers of influenza A virus
复制标题
一种有效的广谱保护性人单克隆抗体，可交联甲型流感病毒的两个血凝素单体
DOI：
10.1038/ncomms8708
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发表时间：
2015-07-01
影响因子：
16.6
通讯作者：
Donis, Ruben O.
中科院分区：
文献类型：
--
作者：
Wu, Ying;Cho, MyungSam;Donis, Ruben O.
有效的年度流感疫苗接种需要经常改变疫苗成分，因为不同亚型血凝素(HAS)的抗原转移和特定HA的抗原漂移。在这里，我们提出了一种具有不同寻常的结合方式的广泛中和的人类单抗。该抗体命名为CT149，是从2009年感染甲型H1N1大流行的康复期患者中分离出来的。CT149被发现通过抑制低pH诱导的HA介导膜融合来中和所有受试的第2组和部分第1组甲型流感病毒。它通过Fc介导的抗体依赖的细胞毒和补体依赖的细胞毒来促进对感染细胞的杀伤。X射线结晶学数据表明，CT149主要与HA2中的融合结构域结合，轻链也主要参与结合。该抗体识别的表位由两个相邻的HA原体的氨基酸残基组成。CT149的这种结合特性将为设计更有效的流感疫苗提供更多信息。
Effective annual influenza vaccination requires frequent changes in vaccine composition due to both antigenic shift for different subtype hemagglutinins (HAs) and antigenic drift in a particular HA. Here we present a broadly neutralizing human monoclonal antibody with an unusual binding modality. The antibody, designated CT149, was isolated from convalescent patients infected with pandemic H1N1 in 2009. CT149 is found to neutralize all tested group 2 and some group 1 influenza A viruses by inhibiting low pH-induced, HA-mediated membrane fusion. It promotes killing of infected cells by Fc-mediated antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. X-ray crystallographic data reveal that CT149 binds primarily to the fusion domain in HA2, and the light chain is also largely involved in binding. The epitope recognized by this antibody comprises amino-acid residues from two adjacent protomers of HA. This binding characteristic of CT149 will provide more information to support the design of more potent influenza vaccines.