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Pre-Clinical Development of a Potent Neutralizing Antibody MW3321 With Extensive SARS-CoV-2 Variants Coverage.
Jiang, Wen; Zhang, Zherui; Zhu, Yuhe; Chen, Ben; Gu, Chunying; Liu, Zhiyan; Zhang, Xukai; Xiong, Hualong; Zhang, Yanan; Zheng, Bin; Wang, Rongjuan; Jiao, Shasha; Wang, An; Zhang, Tianying; Zhang, Jinchao; Wang, Shuang; Zhang, Bo; Li, Gang; Gui, Xun.
Afiliación
  • Jiang W; Mabwell (Shanghai) Bioscience Co., Ltd., Shanghai, China.
  • Zhang Z; Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
  • Zhu Y; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China.
  • Chen B; Mabwell (Shanghai) Bioscience Co., Ltd., Shanghai, China.
  • Gu C; Mabwell (Shanghai) Bioscience Co., Ltd., Shanghai, China.
  • Liu Z; Mabwell (Shanghai) Bioscience Co., Ltd., Shanghai, China.
  • Zhang X; Mabwell (Shanghai) Bioscience Co., Ltd., Shanghai, China.
  • Xiong H; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China.
  • Zhang Y; Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
  • Zheng B; Mabwell (Shanghai) Bioscience Co., Ltd., Shanghai, China.
  • Wang R; Mabwell (Shanghai) Bioscience Co., Ltd., Shanghai, China.
  • Jiao S; Beijing Kohnoor Science and Technology Co., Ltd., Beijing, China.
  • Wang A; Mabwell (Shanghai) Bioscience Co., Ltd., Shanghai, China.
  • Zhang T; Beijing Kohnoor Science and Technology Co., Ltd., Beijing, China.
  • Zhang J; Mabwell (Shanghai) Bioscience Co., Ltd., Shanghai, China.
  • Wang S; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, China.
  • Zhang B; Mabwell (Shanghai) Bioscience Co., Ltd., Shanghai, China.
  • Li G; Mabwell (Shanghai) Bioscience Co., Ltd., Shanghai, China.
  • Gui X; Beijing Kohnoor Science and Technology Co., Ltd., Beijing, China.
Front Pharmacol ; 13: 926750, 2022.
Article en En | MEDLINE | ID: mdl-35873586
Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, several variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged and have consistently replaced the previous dominant variant. Therapeutics against variants of SARS-CoV-2 are urgently needed. Ideal SARS-CoV-2 therapeutic antibodies would have high potency in viral neutralization against several emerging variants. Neutralization antibodies targeting SARS-CoV-2 could provide immediate protection after SARS-CoV-2 infection, especially for the most vulnerable populations. In this work, we comprehensively characterize the breadth and efficacy of SARS-CoV-2 RBD-targeting fully human monoclonal antibody (mAb) MW3321. MW3321 retains full neutralization activity to all tested 12 variants that have arisen in the human population, which are assigned as VOC (Variants of Concern) and VOI (Variants of Interest) due to their impacts on public health. Escape mutation experiments using replicating SARS-CoV-2 pseudovirus show that escape mutants were not generated until passage 6 for MW3321, which is much more resistant to escape mutation compared with another clinical staged SARS-CoV-2 neutralizing mAb MW3311. MW3321 could effectively reduce viral burden in hACE2-transgenic mice challenged with either wild-type or Delta SARS-CoV-2 strains through viral neutralization and Fc-mediated effector functions. Moreover, MW3321 exhibits a typical hIgG1 pharmacokinetic and safety profile in cynomolgus monkeys. These data support the development of MW3321 as a monotherapy or cocktail against SARS-CoV-2-related diseases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Pharmacol Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Pharmacol Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza