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Cross-neutralizing Anti-hemagglutinin Antibodies Isolated from Patients Infected with Avian Influenza A(h5N1) virus

Biomedical and Environmental Sciences 2020年第2期33卷 103-113页

作者： SUN Ying CAO Yang LI Zi BAI Tian ZhANG hong hU Shi Xiong LI Fang Cai ZhAO Xiang ChEN Yong Kun LU Jian LIU Li Qi WANG Da Yan ShU Yue Long ZhOU Jian Fang National Institute for viral Disease Control and Prevention Chinese Center for Disease Control and PreventionKey Laboratory for Medical VirologyNational Health and Family Planning CommissionBeijing 102206China Center of Growth Metabolism and AgingKey Laboratory of Bio-Resource and Eco-EnvironmentMinistry of EducationCollege of Life SciencesSichuan UniversityChengdu 610064SichuanChina hunan Provincial Disease Control and Prevention Changsha 410000HunanChina School of Public health(Shenzhen) Sun Yatsen UniversityShenzhen 510275GuangdongChina

Objective To recover broad-neutralizing monoclonal antibodies(Bn Abs)from avian influenza A(h5N1)virus infection cases and investigate their genetic and functional *** We screened the Abs repertoires of expanded B cells circulating in the peripheral blood of h5N1 *** genetic basis,biological functions,and epitopes of the obtained Bn Abs were assessed and *** Two Bn Abs,2-12 D5,and 3-37 G7.1,were respectively obtained from two human h5N1 cases on days 12 and 21 after disease *** Abs demonstrated cross-neutralizing and Ab-dependent cellular cytotoxicity(ADCC)*** derived from distinct Ab lineages,i.e.,v^h1-69-D2-15-Jh^4(2-12D5)and v^h1-2-D3-9-Jh^5(3-32 G7.1),the Bn Abs were directed toward CR6261-like epitopes in the hA stem,and hA2 I45 in the hydrophobic pocket was the critical residue for their *** motifs for binding with the hA stem,namely,IFY in vh1-69-encoded Abs and LXYFXW in D3-9-encoded Abs,were also observed in 2-12D5 and 3-32 G7.1,*** Cross-reactive B cells of different germline origins could be activated and re-circulated by avian influenza *** hA stem epitopes targeted by the Bn Abs,and the two Ab-encoding genes usage implied the vh1-69 and D3-9 are the ideal candidates triggered by influenza virus for vaccine development.

关键词： v^h1-69 D3-9 Avian influenza A(h5N1)virus Cross-neutralizing Antibody

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