A Potent Germline-like Human Monoclonal Antibody Targets a pH-Sensitive Epitope on H7N9 Influenza Hemagglutinin.
A Potent Germline-like Human Monoclonal Antibody Targets a pH-Sensitive Epitope on H7N9 Influenza Hemagglutinin.
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一种有效的种系样人单克隆抗体靶向 H7N9 流感血凝素上的 pH 敏感表位
DOI：
10.1016/j.chom.2017.08.011
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发表时间：
2017-10-11
影响因子：
30.3
通讯作者：
Ying T
中科院分区：
文献类型：
--
作者：
Yu F;Song H;Wu Y;Chang SY;Wang L;Li W;Hong B;Xia S;Wang C;Khurana S;Feng Y;Wang Y;Sun Z;He B;Hou D;Manischewitz J;King LR;Song Y;Min JY;Golding H;Ji X;Lu L;Jiang S;Dimitrov DS;Ying T
H7N9流感病毒在人类中引起高肌肉疾病，但在这里没有有效的疗法。 M826的晶体结构与H7N9 HA复合表明M826可以通过pH诱导的HA构造变化来完全暴露于M826的构造变化，从而通过可能涉及抗体依赖性细胞介导的细胞毒性的人物识别M826 semelliese HON726-semline Antliby-nylline Antbody suby semine and and and-and-and-and-andib semline Antbody，它可以通过H7N9病毒进行致命的挑战。 s，和这些新生婴儿。这些M826特性为H7N9疫苗免疫剂，承诺候选疗法提供了模板，并提供了一种探索抗体抑制病毒感染机制的工具。
结合H7N9 HA的人类种系单克隆抗体（M826）的鉴定
H7N9 HA的结构与M826抗体复合
抗体识别H7N9 HA中的pH敏感性表位
抗体完全保护小鼠免受H7N9病毒的致命挑战
H7N9在人类中会导致人类的疾病。
The H7N9 influenza virus causes high-mortality disease in humans but no effective therapeutics are available. Here we report a human monoclonal antibody, m826, that binds to H7 hemagglutinin (HA) and protects against H7N9 infection. m826 binds to H7N9 HA with subnanomolar affinity at acidic pH and 10-fold lower affinity at neutral pH. The high-resolution (1.9 Å) crystal structure of m826 complexed with H7N9 HA indicates that m826 binds an epitope that may be fully exposed upon pH-induced conformational changes in HA. m826 fully protects mice against lethal challenge with H7N9 virus through mechanisms likely involving antibody-dependent cell-mediated cytotoxicity. Interestingly, immunogenetic analysis indicates that m826 is a germline antibody, and m826-like sequences can be identified in H7N9-infected patients, healthy adults, and newborn babies. These m826 properties offer a template for H7N9 vaccine immunogens, a promising candidate therapeutic, and a tool for exploring mechanisms of virus infection inhibition by antibodies. Identification of human germline monoclonal antibody (m826) that binds H7N9 HA Structure of H7N9 HA complexed with m826 antibody Antibody recognizes a pH-sensitive epitope within H7N9 HA Antibody fully protects mice against lethal challenge with H7N9 virus H7N9 influenza virus causes high-mortality disease in humans. Yu et al. identify a human germline monoclonal antibody recognizing a pH-sensitive epitope on H7N9 hemagglutinin globular head. This antibody is effective against H7N9 influenza in vivo, likely due to ADCC activity, and may facilitate the development of prophylactics and therapeutics.
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影响因子：
64.8
作者：
Huang J;Ofek G;Laub L;Louder MK;Doria-Rose NA;Longo NS;Imamichi H;Bailer RT;Chakrabarti B;Sharma SK;Alam SM;Wang T;Yang Y;Zhang B;Migueles SA;Wyatt R;Haynes BF;Kwong PD;Mascola JR;Connors M
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Connors M
人类感染新型禽源甲型流感 (H7N9) 病毒。
影响因子：
158.5
作者：
Gao, Rongbao;Cao, Bin;Shu, Yuelong
通讯作者：
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影响因子：
5.3
作者：
Feng, Yang;Wang, Yanping;Dimitrov, Dimiter S.
通讯作者：
Dimitrov, Dimiter S.
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。
影响因子：
30.3
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
通讯作者：
Wilson PC
影响因子：
64.5
作者：
Bonsignori M;Zhou T;Sheng Z;Chen L;Gao F;Joyce MG;Ozorowski G;Chuang GY;Schramm CA;Wiehe K;Alam SM;Bradley T;Gladden MA;Hwang KK;Iyengar S;Kumar A;Lu X;Luo K;Mangiapani MC;Parks RJ;Song H;Acharya P;Bailer RT;Cao A;Druz A;Georgiev IS;Kwon YD;Louder MK;Zhang B;Zheng A;Hill BJ;Kong R;Soto C;NISC Comparative Sequencing Program;Mullikin JC;Douek DC;Montefiori DC;Moody MA;Shaw GM;Hahn BH;Kelsoe G;Hraber PT;Korber BT;Boyd SD;Fire AZ;Kepler TB;Shapiro L;Ward AB;Mascola JR;Liao HX;Kwong PD;Haynes BF
通讯作者：
Haynes BF