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Bispecific antibodies with broad neutralization potency against SARS-CoV-2 variants of concern.
Rubio, Adonis A; Baharani, Viren A; Dadonaite, Bernadeta; Parada, Megan; Abernathy, Morgan E; Wang, Zijun; Lee, Yu E; Eso, Michael R; Phung, Jennie; Ramos, Israel; Chen, Teresia; Nesr, Gina El; Bloom, Jesse D; Bieniasz, Paul D; Nussenzweig, Michel C; Barnes, Christopher O.
Afiliación
  • Rubio AA; Stanford Biosciences, Stanford School of Medicine; Stanford, USA.
  • Baharani VA; Department of Biology, Stanford University; Stanford, USA.
  • Dadonaite B; Laboratory of Retrovirology, The Rockefeller University; New York, USA.
  • Parada M; Laboratory of Molecular Immunology, The Rockefeller University; New York, USA.
  • Abernathy ME; Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center; Seattle, USA.
  • Wang Z; Department of Biology, Stanford University; Stanford, USA.
  • Lee YE; Department of Biology, Stanford University; Stanford, USA.
  • Eso MR; Laboratory of Molecular Immunology, The Rockefeller University; New York, USA.
  • Phung J; Department of Biology, Stanford University; Stanford, USA.
  • Ramos I; Department of Biology, Stanford University; Stanford, USA.
  • Chen T; Department of Biology, Stanford University; Stanford, USA.
  • Nesr GE; Department of Biology, Stanford University; Stanford, USA.
  • Bloom JD; Department of Biology, Stanford University; Stanford, USA.
  • Bieniasz PD; Stanford Biosciences, Stanford School of Medicine; Stanford, USA.
  • Nussenzweig MC; Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center; Seattle, USA.
  • Barnes CO; Howard Hughes Medical Institute; Chevy Chase, USA.
bioRxiv ; 2024 May 06.
Article en En | MEDLINE | ID: mdl-38766244
ABSTRACT
The ongoing emergence of SARS-CoV-2 variants of concern (VOCs) that reduce the effectiveness of antibody therapeutics necessitates development of next-generation antibody modalities that are resilient to viral evolution. Here, we characterized N-terminal domain (NTD) and receptor binding domain (RBD)-specific monoclonal antibodies previously isolated from COVID-19 convalescent donors for their activity against emergent SARS-CoV-2 VOCs. Among these, the NTD-specific antibody C1596 displayed the greatest breadth of binding to VOCs, with cryo-EM structural analysis revealing recognition of a distinct NTD epitope outside of the site i antigenic supersite. Given C1596's favorable binding profile, we designed a series of bispecific antibodies (bsAbs) termed CoV2-biRNs, that featured both NTD and RBD specificities. Notably, two of the C1596-inclusive bsAbs, CoV2-biRN5 and CoV2-biRN7, retained potent in vitro neutralization activity against all Omicron variants tested, including XBB.1.5, EG.5.1, and BA.2.86, contrasting the diminished potency of parental antibodies delivered as monotherapies or as a cocktail. Furthermore, prophylactic delivery of CoV2-biRN5 significantly reduced the viral load within the lungs of K18-hACE2 mice following challenge with SARS-CoV-2 XBB.1.5. In conclusion, our NTD-RBD bsAbs offer promising potential for the design of resilient, next-generation antibody therapeutics against SARS-CoV-2 VOCs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos