Cross-neutralizing Anti-hemagglutinin Antibodies Isolated from Patients Infected with Avian Influenza A(H5N1) Virus  

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 

机构地区：[1]National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Key Laboratory for Medical Virology,National Health and Family Planning Commission,Beijing 102206,China [2]Center of Growth,Metabolism and Aging,Key Laboratory of Bio-Resource and Eco-Environment,Ministry of Education,College of Life Sciences,Sichuan University,Chengdu 610064,Sichuan,China [3]Hunan Provincial Disease Control and Prevention,Changsha 410000,Hunan,China [4]School of Public Health(Shenzhen),Sun Yatsen University,Shenzhen 510275,Guangdong,China

出　　处：《Biomedical and Environmental Sciences》2020年第2期103-113,共11页生物医学与环境科学（英文版）

基　　金：supported by the General Program of the National Natural Science Foundation of China[No.31570162];the National Key Research Program[No.2016YFC1200200].

摘　　要：Objective To recover broad-neutralizing monoclonal antibodies(Bn Abs)from avian influenza A(H5N1)virus infection cases and investigate their genetic and functional features.Methods We screened the Abs repertoires of expanded B cells circulating in the peripheral blood of H5N1 patients.The genetic basis,biological functions,and epitopes of the obtained Bn Abs were assessed and modeled.Results 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 onset.Both Abs demonstrated cross-neutralizing and Ab-dependent cellular cytotoxicity(ADCC)activity.Albeit 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 binding.Signature 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,respectively.Conclusions Cross-reactive B cells of different germline origins could be activated and re-circulated by avian influenza virus.The 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.Objective To recover broad-neutralizing monoclonal antibodies（Bn Abs） from avian influenza A（H5N1）virus infection cases and investigate their genetic and functional features.Methods We screened the Abs repertoires of expanded B cells circulating in the peripheral blood of H5N1 patients.The genetic basis,biological functions,and epitopes of the obtained Bn Abs were assessed and modeled.Results 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 onset.Both Abs demonstrated cross-neutralizing and Ab-dependent cellular cytotoxicity（ADCC） activity.Albeit derived from distinct Ab lineages,i.e.,VH1-69-D2-15-JH4（2-12D5） and VH1-2-D3-9-JH5（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 binding.Signature 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,respectively.Conclusions Cross-reactive B cells of different germline origins could be activated and re-circulated by avian influenza virus.The 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 

分 类 号：R511.7[医药卫生—内科学]