A potent broad-spectrum protective human monoclonal antibody crosslinking two haemagglutinin monomers of influenza A virus

Ying Wu, MyungSam Cho, David Shore, Manki Song, JungAh Choi, Tao Jiang, Yong-Qiang Deng, Melissa Bourgeois, Lynn Almli, Hua Yang, Li-Mei Chen, Yi Shi, Jianxu Qi, An Li, Kye Sook Yi, MinSeok Chang, Jin Soo Bae, HyunJoo Lee, JiYoung Shin, James Stevens, SeoungSuh Hong, Cheng-Feng Qin (), George F. Gao (), Shin Jae Chang () and Ruben O. Donis ()
Additional contact information
Ying Wu: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
MyungSam Cho: Biotechnology Research Institute, Celltrion, Inc.
David Shore: Centers for Disease Control and Prevention
Manki Song: International Vaccine Institute
JungAh Choi: International Vaccine Institute
Tao Jiang: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology
Yong-Qiang Deng: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology
Melissa Bourgeois: Centers for Disease Control and Prevention
Lynn Almli: Centers for Disease Control and Prevention
Hua Yang: Centers for Disease Control and Prevention
Li-Mei Chen: Centers for Disease Control and Prevention
Yi Shi: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Jianxu Qi: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
An Li: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Kye Sook Yi: Biotechnology Research Institute, Celltrion, Inc.
MinSeok Chang: Biotechnology Research Institute, Celltrion, Inc.
Jin Soo Bae: Biotechnology Research Institute, Celltrion, Inc.
HyunJoo Lee: Biotechnology Research Institute, Celltrion, Inc.
JiYoung Shin: Biotechnology Research Institute, Celltrion, Inc.
James Stevens: Centers for Disease Control and Prevention
SeoungSuh Hong: Biotechnology Research Institute, Celltrion, Inc.
Cheng-Feng Qin: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology
George F. Gao: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Shin Jae Chang: Biotechnology Research Institute, Celltrion, Inc.
Ruben O. Donis: Centers for Disease Control and Prevention

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: Abstract Effective annual influenza vaccination requires frequent changes in vaccine composition due to both antigenic shift for different subtype hemagglutinins (HAs) and antigenic drift in a particular HA. Here we present a broadly neutralizing human monoclonal antibody with an unusual binding modality. The antibody, designated CT149, was isolated from convalescent patients infected with pandemic H1N1 in 2009. CT149 is found to neutralize all tested group 2 and some group 1 influenza A viruses by inhibiting low pH-induced, HA-mediated membrane fusion. It promotes killing of infected cells by Fc-mediated antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. X-ray crystallographic data reveal that CT149 binds primarily to the fusion domain in HA2, and the light chain is also largely involved in binding. The epitope recognized by this antibody comprises amino-acid residues from two adjacent protomers of HA. This binding characteristic of CT149 will provide more information to support the design of more potent influenza vaccines.

Date: 2015
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DOI: 10.1038/ncomms8708

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