title: Potent neutralizing monoclonal antibodies against Ebola virus infection.
abstract: Ebola virus infections cause a deadly hemorrhagic disease for which no vaccines or therapeutics has received regulatory approval. Here we show isolation of three (Q206, Q314 and Q411) neutralizing monoclonal antibodies (mAbs) against the surface glycoprotein (GP) of Ebola virus identified in West Africa in 2014 through sequential immunization of Chinese rhesus macaques and antigen-specific single B cell sorting. These mAbs demonstrated potent neutralizing activities against both pseudo and live Ebola virus independent of complement. Biochemical, single particle EM, and mutagenesis analysis suggested Q206 and Q411 recognized novel epitopes in the head while Q314 targeted the glycan cap in the GP1 subunit. Q206 and Q411 appeared to influence GP binding to its receptor NPC1. Treatment with these mAbs provided partial but significant protection against disease in a mouse model of Ebola virus infection. These novel mAbs could serve as promising candidates for prophylactic and therapeutic interventions against Ebola virus infection.
authors.affiliation: Comprehensive AIDS Research Center, and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Beijing Advanced Innovation Center for Structure Biology, and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Gui
authors.affiliation: State Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Niu
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, R3E 3R2 Canada.|Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, R3E 0J9 Canada.
authors.forename: Shihua
authors.initials: S
authors.lastname: He
authors.affiliation: Comprehensive AIDS Research Center, and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Ruoke
authors.initials: R
authors.lastname: Wang
authors.affiliation: Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, R3E 3R2 Canada.|Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, R3E 0J9 Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kroeker
authors.affiliation: Comprehensive AIDS Research Center, and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: Comprehensive AIDS Research Center, and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Comprehensive AIDS Research Center, and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Comprehensive AIDS Research Center, and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Jiade
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, China.
authors.forename: Chufang
authors.initials: C
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology and Research Network of Immunity and Health, and Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Comprehensive AIDS Research Center, and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Xuanling
authors.initials: X
authors.lastname: Shi
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology and Research Network of Immunity and Health, and Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
authors.affiliation: Beijing Advanced Innovation Center for Structure Biology, and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, R3E 3R2 Canada.|Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, R3E 0J9 Canada.
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, China.|Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Comprehensive AIDS Research Center, and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Linqi
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000302:isolation & purification* / Q000494:pharmacology; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D029043:Ebolavirus / Q000187:drug effects / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control*; D007116:Immunization, Passive; D008253:Macaca mulatta / Q000276:immunology* / Q000821:virology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D014611:Vaccination
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D008562:Membrane Glycoproteins