Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that causes substantial morbidity and mortality in livestock and humans. To date, there are no licensed human vaccines or therapeutics available. Here, we report the isolation of monoclonal antibodies from a convalescent patient, targeting the RVFV envelope proteins Gn and Gc. The Gn-specific monoclonal antibodies exhibited much higher neutralizing activities in vitro and protection efficacies in mice against RVFV infection, compared to the Gc-specific monoclonal antibodies. The Gn monoclonal antibodies were found to interfere with soluble Gn binding to cells and prevent infection by blocking the attachment of virions to host cells. Structural analysis of Gn complexed with four Gn-specific monoclonal antibodies resulted in the definition of three antigenic patches (A, B and C) on Gn domain I. Both patches A and B are major neutralizing epitopes. Our results highlight the potential of antibody-based therapeutics and provide a structure-based rationale for designing vaccines against RVFV.
Organizational Affiliation:
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen, China.
Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
Institute of Physical Science and Information, Anhui University, Hefei, China.
Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.
Center of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Département de Microbiologie-Infectiologie et d'Immunologie, Université Laval, Quebec, Quebec, Canada.
Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
College of Veterinary Medicine, China Agricultural University, Beijing, China.
Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control, Beijing, China.
International Laboratory of Molecular Biology for Tropical Disease Agents, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, CA, USA.
Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing, China.
Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health, Institute of Medical Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China.
Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen, China. gaof@im.ac.cn.
Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China. gaof@im.ac.cn.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. gaof@im.ac.cn.
College of Veterinary Medicine, China Agricultural University, Beijing, China. gaof@im.ac.cn.
Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China. gaof@im.ac.cn.
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing, China. gaof@im.ac.cn.
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China. gaof@im.ac.cn.
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. yanjh@im.ac.cn.
Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen, China. yanjh@im.ac.cn.
Institute of Physical Science and Information, Anhui University, Hefei, China. yanjh@im.ac.cn.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. yanjh@im.ac.cn.
College of Life Science, University of Chinese Academy of Sciences, Beijing, China. yanjh@im.ac.cn.
Download Mendeley
