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

Ying SUN; Yang CAO; Zi LI; Tian BAI; Hong ZHANG; Shi Xiong HU; Fang Cai LI; Xiang ZHAO; Yong Kun CHEN; Jian LU; Li Qi LIU; Da Yan WANG; Yue Long SHU; Jian Fang ZHOU

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

Author: Ying SUN ¹ ; Yang CAO ² ; Zi LI ¹ ; Tian BAI ¹ ; Hong ZHANG ³ ; Shi Xiong HU ³ ; Fang Cai LI ³ ; Xiang ZHAO ¹ ; Yong Kun CHEN ⁴ ; Jian LU ¹ ; Li Qi LIU ¹ ; Da Yan WANG ¹ ; Yue Long SHU ⁴ ; Jian Fang ZHOU ¹
Author Information

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. 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;School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 510275, Guangdong, China.
Publication Type:Journal Article
Keywords: Antibody; Avian influenza A (H5N1) virus; Cross-neutralizing; D3-9; VH1-69
From: Biomedical and Environmental Sciences 2020;33(2):103-113
CountryChina
Language:English
Abstract: Objective:To recover broad-neutralizing monoclonal antibodies (BnAbs) 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 BnAbs were assessed and modeled.
Results:Two BnAbs, 2-12D5, and 3-37G7.1, 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, , V 1-69-D2-15-J 4 (2-12D5) and V 1-2-D3-9-J 5 (3-32G7.1), the BnAbs were directed toward CR6261-like epitopes in the HA stem, and HA I45 in the hydrophobic pocket was the critical residue for their binding. Signature motifs for binding with the HA stem, namely, IFY in V 1-69-encoded Abs and LXYFXW in D3-9-encoded Abs, were also observed in 2-12D5 and 3-32G7.1, 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 BnAbs, 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.