Your browser doesn't support javascript.
loading
Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617.
Peng, Lei; Hu, Yingxia; Mankowski, Madeleine C; Ren, Ping; Chen, Rita E; Wei, Jin; Zhao, Min; Li, Tongqing; Tripler, Therese; Ye, Lupeng; Chow, Ryan D; Fang, Zhenhao; Wu, Chunxiang; Dong, Matthew B; Cook, Matthew; Wang, Guilin; Clark, Paul; Nelson, Bryce; Klein, Daryl; Sutton, Richard; Diamond, Michael S; Wilen, Craig B; Xiong, Yong; Chen, Sidi.
Afiliação
  • Peng L; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
  • Hu Y; System Biology Institute, Yale University, West Haven, CT, USA.
  • Mankowski MC; Center for Cancer Systems Biology, Yale University, West Haven, CT, USA.
  • Ren P; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
  • Chen RE; Department of Laboratory Medicine, Yale University, New Haven, CT, USA.
  • Wei J; Department of Immunobiology, Yale University, New Haven, CT, USA.
  • Zhao M; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
  • Li T; System Biology Institute, Yale University, West Haven, CT, USA.
  • Tripler T; Center for Cancer Systems Biology, Yale University, West Haven, CT, USA.
  • Ye L; Departments of Medicine and Pathology & Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
  • Chow RD; Department of Laboratory Medicine, Yale University, New Haven, CT, USA.
  • Fang Z; Department of Immunobiology, Yale University, New Haven, CT, USA.
  • Wu C; Section of Infectious Diseases, Department of Internal Medicine, Yale University, New Haven, CT, USA.
  • Dong MB; Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA.
  • Cook M; Cancer Biology Institute, Yale University, West Haven, CT, USA.
  • Wang G; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
  • Clark P; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
  • Nelson B; System Biology Institute, Yale University, West Haven, CT, USA.
  • Klein D; Center for Cancer Systems Biology, Yale University, West Haven, CT, USA.
  • Sutton R; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
  • Diamond MS; System Biology Institute, Yale University, West Haven, CT, USA.
  • Wilen CB; Center for Cancer Systems Biology, Yale University, West Haven, CT, USA.
  • Xiong Y; M.D.-Ph.D. Program, Yale University, West Haven, CT, USA.
  • Chen S; Molecular Cell Biology, Genetics, and Development Program, Yale University, New Haven, CT, USA.
bioRxiv ; 2021 Dec 24.
Article em En | MEDLINE | ID: mdl-34981065
ABSTRACT
COVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging variants. Effective therapeutic options such as monoclonal antibodies (mAbs) are still critical. Here, we report the development, cryo-EM structures, and functional analyses of mAbs that potently neutralize SARS-CoV-2 variants of concern. By high-throughput single cell sequencing of B cells from spike receptor binding domain (RBD) immunized animals, we identified two highly potent SARS-CoV-2 neutralizing mAb clones that have single-digit nanomolar affinity and low-picomolar avidity, and generated a bispecific antibody. Lead antibodies showed strong inhibitory activity against historical SARS-CoV-2 and several emerging variants of concern. We solved several cryo-EM structures at ∼3 Šresolution of these neutralizing antibodies in complex with prefusion spike trimer ectodomain, and revealed distinct epitopes, binding patterns, and conformations. The lead clones also showed potent efficacy in vivo against authentic SARS-CoV-2 in both prophylactic and therapeutic settings. We also generated and characterized a humanized antibody to facilitate translation and drug development. The humanized clone also has strong potency against both the original virus and the B.1.617.2 Delta variant. These mAbs expand the repertoire of therapeutics against SARS-CoV-2 and emerging variants.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: BioRxiv Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: BioRxiv Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos