A common solution to group 2 influenza virus neutralization
A common solution to group 2 influenza virus neutralization
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DOI：
10.1073/pnas.1319058110
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发表时间：
2014-01-07
影响因子：
11.1
通讯作者：
Wilson, Ian A.
中科院分区：
文献类型：
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作者：
Friesen, Robert H. E.;Lee, Peter S.;Wilson, Ian A.
针对流感病毒的广泛中和抗体（bnAbs）的发现和特性研究为基于单克隆抗体（mAb）的免疫疗法的开发以及通用流感疫苗的设计带来了希望。此前仅有1种特异性识别甲型流感病毒第2组的人源广泛中和抗体（CR8020）被鉴定出来，它与血凝素（HA）茎部底部的一个高度保守表位结合，对H3、H7和H10病毒具有中和活性。在此，我们报道了第2种第2组广泛中和抗体CR8043，它源自编码一种高度不同氨基酸序列的不同种系基因。CR8043对H3和H10病毒具有体外中和活性，并能保护小鼠免受致死剂量的H3N2和H7N7病毒的攻击。CR8043 - H3 HA复合物的晶体结构和电镜重建显示，CR8043结合在一个与CR8020表位相似的位点，但采用了不同的接近角度和一组独特的相互作用。另一种针对第2组茎部表位的抗体的鉴定表明，这个保守的易受攻击位点在治疗药物和疫苗设计方面具有巨大潜力。
The discovery and characterization of broadly neutralizing antibodies (bnAbs) against influenza viruses have raised hopes for the development of monoclonal antibody (mAb)-based immunotherapy and the design of universal influenza vaccines. Only one human bnAb (CR8020) specifically recognizing group 2 influenza A viruses has been previously characterized that binds to a highly conserved epitope at the base of the hemagglutinin (HA) stem and has neutralizing activity against H3, H7, and H10 viruses. Here, we report a second group 2 bnAb, CR8043, which was derived from a different germ-line gene encoding a highly divergent amino acid sequence. CR8043 has in vitro neutralizing activity against H3 and H10 viruses and protects mice against challenge with a lethal dose of H3N2 and H7N7 viruses. The crystal structure and EM reconstructions of the CR8043-H3 HA complex revealed that CR8043 binds to a site similar to the CR8020 epitope but uses an alternative angle of approach and a distinct set of interactions. The identification of another antibody against the group 2 stem epitope suggests that this conserved site of vulnerability has great potential for design of therapeutics and vaccines.