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Bispecific antibodies targeting two glycoproteins on SFTSV exhibit synergistic neutralization and protection in a mouse model.
Chang, Zhen; Gao, Dan; Liao, Liying; Sun, Junqing; Zhang, Gen; Zhang, Xue; Wang, Feiran; Li, Chunrui; Oladejo, Babayemi Olawale; Li, Shihua; Chai, Yan; Hu, Yongfei; Lu, Xuancheng; Xiao, Haixia; Qi, Jianxun; Chen, Zhihai; Gao, Feng; Wu, Yan.
  • Chang Z; Department of Pathogen Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
  • Gao D; Department of Pathogen Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
  • Liao L; Department of Pathogen Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
  • Sun J; Chinese Academy of Sciences Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  • Zhang G; College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, Shanxi 030801, China.
  • Zhang X; Chinese Academy of Sciences Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  • Wang F; Faculty of Health Sciences, University of Macau, Macau SAR 999078, China.
  • Li C; Department of Pathogen Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
  • Oladejo BO; Chinese Academy of Sciences Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  • Li S; Chinese Academy of Sciences Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  • Chai Y; Chinese Academy of Sciences Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  • Hu Y; Department of Microbiology, Federal University of Technology, PMB704, Akure, Nigeria.
  • Lu X; Chinese Academy of Sciences Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  • Xiao H; Chinese Academy of Sciences Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  • Qi J; College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
  • Chen Z; National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
  • Gao F; Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
  • Wu Y; Chinese Academy of Sciences Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Proc Natl Acad Sci U S A ; 121(24): e2400163121, 2024 Jun 11.
Article en En | MEDLINE | ID: mdl-38830098
ABSTRACT
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high fatality rate of up to 30% caused by SFTS virus (SFTSV). However, no specific vaccine or antiviral therapy has been approved for clinical use. To develop an effective treatment, we isolated a panel of human monoclonal antibodies (mAbs). SF5 and SF83 are two neutralizing mAbs that recognize two viral glycoproteins (Gn and Gc), respectively. We found that their epitopes are closely located, and we then engineered them as several bispecific antibodies (bsAbs). Neutralization and animal experiments indicated that bsAbs display more potent protective effects than the parental mAbs, and the cryoelectron microscopy structure of a bsAb3 Fab-Gn-Gc complex elucidated the mechanism of protection. In vivo virus passage in the presence of antibodies indicated that two bsAbs resulted in less selective pressure and could efficiently bind to all single parental mAb-escape mutants. Furthermore, epitope analysis of the protective mAbs against SFTSV and RVFV indicated that they are all located on the Gn subdomain I, where may be the hot spots in the phleboviruses. Collectively, these data provide potential therapeutic agents and molecular basis for the rational design of vaccines against SFTSV infection.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Phlebovirus / Anticuerpos Biespecíficos / Anticuerpos Neutralizantes / Anticuerpos Antivirales Límite: Animals / Humans Idioma: En Año: 2024 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Phlebovirus / Anticuerpos Biespecíficos / Anticuerpos Neutralizantes / Anticuerpos Antivirales Límite: Animals / Humans Idioma: En Año: 2024 Tipo del documento: Article