title: A potent broad-spectrum protective human monoclonal antibody crosslinking two haemagglutinin monomers of influenza A virus.
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.
authors.affiliation: 1] CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, No. 1 West Beichen Road, Beijing 100101, China. [2] Center for Influenza Research and Early-warning, Chinese Academy of Sciences, No. 1 West Beichen Road, Beijing 100101, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Biotechnology Research Institute, Celltrion, Inc., Incheon 406-840, South Korea.
authors.forename: MyungSam
authors.initials: M
authors.lastname: Cho
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
authors.forename: David
authors.initials: D
authors.lastname: Shore
authors.affiliation: International Vaccine Institute, Seoul 151-919, South Korea.
authors.forename: Manki
authors.initials: M
authors.lastname: Song
authors.affiliation: International Vaccine Institute, Seoul 151-919, South Korea.
authors.forename: JungAh
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Deng
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Bourgeois
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Almli
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Chen
authors.affiliation: 1] CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, No. 1 West Beichen Road, Beijing 100101, China. [2] Center for Influenza Research and Early-warning, Chinese Academy of Sciences, No. 1 West Beichen Road, Beijing 100101, China. [3] Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, No. 1 West Beichen Road, Beijing 100101, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.affiliation: 1] CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, No. 1 West Beichen Road, Beijing 100101, China. [2] Center for Influenza Research and Early-warning, Chinese Academy of Sciences, No. 1 West Beichen Road, Beijing 100101, China.
authors.forename: Jianxu
authors.initials: J
authors.lastname: Qi
authors.affiliation: 1] CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, No. 1 West Beichen Road, Beijing 100101, China. [2] College of Veterinary Medicine, Guangxi University, Nanning 530004, China.
authors.forename: An
authors.initials: A
authors.lastname: Li
authors.affiliation: Biotechnology Research Institute, Celltrion, Inc., Incheon 406-840, South Korea.
authors.forename: Kye Sook
authors.initials: KS
authors.lastname: Yi
authors.affiliation: Biotechnology Research Institute, Celltrion, Inc., Incheon 406-840, South Korea.
authors.forename: MinSeok
authors.initials: M
authors.lastname: Chang
authors.affiliation: Biotechnology Research Institute, Celltrion, Inc., Incheon 406-840, South Korea.
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Bae
authors.affiliation: Biotechnology Research Institute, Celltrion, Inc., Incheon 406-840, South Korea.
authors.forename: HyunJoo
authors.initials: H
authors.lastname: Lee
authors.affiliation: Biotechnology Research Institute, Celltrion, Inc., Incheon 406-840, South Korea.
authors.forename: JiYoung
authors.initials: J
authors.lastname: Shin
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
authors.forename: James
authors.initials: J
authors.lastname: Stevens
authors.affiliation: Biotechnology Research Institute, Celltrion, Inc., Incheon 406-840, South Korea.
authors.forename: SeoungSuh
authors.initials: S
authors.lastname: Hong
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Cheng-Feng
authors.identifier: 0000000206322807
authors.initials: CF
authors.lastname: Qin
authors.affiliation: 1] CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, No. 1 West Beichen Road, Beijing 100101, China. [2] Center for Influenza Research and Early-warning, Chinese Academy of Sciences, No. 1 West Beichen Road, Beijing 100101, China. [3] Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, No. 1 West Beichen Road, Beijing 100101, China. [4] Office of Director-General, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China.
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
authors.affiliation: Biotechnology Research Institute, Celltrion, Inc., Incheon 406-840, South Korea.
authors.forename: Shin Jae
authors.initials: SJ
authors.lastname: Chang
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
authors.forename: Ruben O
authors.initials: RO
authors.lastname: Donis
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004285:Dogs; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines; D061985:Madin Darby Canine Kidney Cells; D008807:Mice, Inbred BALB C
chemical_list: D000911:Antibodies, Monoclonal; C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines