Antibody 27F3 Broadly Targets Influenza A Group 1 and 2 Hemagglutinins through a Further Variation in V(H)1-69 Antibody Orientation on the HA Stem.
Antibody 27F3 Broadly Targets Influenza A Group 1 and 2 Hemagglutinins through a Further Variation in V(H)1-69 Antibody Orientation on the HA Stem.
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DOI：
10.1016/j.celrep.2017.08.084
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发表时间：
2017-09-19
期刊：
影响因子：
8.8
通讯作者：
Wilson IA
中科院分区：
文献类型：
--
作者：
Lang S;Xie J;Zhu X;Wu NC;Lerner RA;Wilson IA
靶向第1组和第2组甲型流感病毒的抗体对于治疗和疫苗开发是有价值的，但迄今为止只有少数报道。在这里，我们描述了一种新的VH 1 -69抗体27 F3，广泛识别来自组1和组2甲型流感病毒的异亚型HA。27 F3 Fab与A/加州/04/2009（H1N1）血凝素的结构表征说明27 F3与HA茎的其他VH 1 -69抗体中观察到的关键特征相同。与其他VH 1 -69抗体相比，27 F3 VH结构域以不同的方向与HA茎相互作用，这改变了其表位并可能影响其宽度。VH 1 -69抗体在HA茎表位上的不同旋转突出了该抗体家族可以进化以广泛中和甲型流感病毒的不同方式。这些结果对于理解如何引起针对流感病毒的广泛抗体应答具有重要意义。Lang等人发现了一种中和组1和组2甲型流感病毒的人VH 1 -69抗体，并证明了这类抗体与HA茎的结合模式的一致性和差异。
Antibodies that target both group 1 and group 2 influenza A viruses are valuable for therapeutic and vaccine development, but only a few have been reported to date. Here we describe a new VH1-69 antibody 27F3 that broadly recognizes heterosubtypic HAs from both group 1 and group 2 influenza A viruses. Structural characterization of 27F3 Fab with A/California/04/2009 (H1N1) hemagglutinin illustrates 27F3 shares the key features observed in other VH1-69 antibodies to the HA stem. Compared to other VH1-69 antibodies, the 27F3 VH domain interacts with the HA stem in a distinct orientation, which alters its epitope and may have influenced its breadth. The diverse rotations of VH1-69 antibodies on the HA stem epitope highlight the different ways that this antibody family can evolve to broadly neutralize influenza A viruses. These results have important implications for understanding how to elicit broad antibody responses against influenza virus. Lang et al. uncover a human VH1-69 antibody that neutralizes group 1 and group 2 influenza A viruses and demonstrate the consensus and differences in the mode of binding of antibodies from this class with the HA stem.
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影响因子：
30.3
作者：
Das, Suman R.;Hensley, Scott E.;Yewdell, Jonathan W.
通讯作者：
Yewdell, Jonathan W.
DOI：
10.1073/pnas.1319058110
发表时间：
2014-01-07
影响因子：
11.1
作者：
Friesen, Robert H. E.;Lee, Peter S.;Wilson, Ian A.
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影响因子：
64.5
作者：
Garces F;Sok D;Kong L;McBride R;Kim HJ;Saye-Francisco KF;Julien JP;Hua Y;Cupo A;Moore JP;Paulson JC;Ward AB;Burton DR;Wilson IA
通讯作者：
Wilson IA
影响因子：
7.6
作者：
Laursen, Nick S.;Wilson, Ian A.
通讯作者：
Wilson, Ian A.
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH