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Development of potency, breadth and resilience to viral escape mutations in SARS-CoV-2 neutralizing antibodies.
Muecksch, Frauke; Weisblum, Yiska; Barnes, Christopher O; Schmidt, Fabian; Schaefer-Babajew, Dennis; Lorenzi, Julio C C; Flyak, Andrew I; DeLaitsch, Andrew T; Huey-Tubman, Kathryn E; Hou, Shurong; Schiffer, Celia A; Gaebler, Christian; Wang, Zijun; Da Silva, Justin; Poston, Daniel; Finkin, Shlomo; Cho, Alice; Cipolla, Melissa; Oliveira, Thiago Y; Millard, Katrina G; Ramos, Victor; Gazumyan, Anna; Rutkowska, Magdalena; Caskey, Marina; Nussenzweig, Michel C; Bjorkman, Pamela J; Hatziioannou, Theodora; Bieniasz, Paul D.
Afiliación
  • Muecksch F; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.
  • Weisblum Y; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.
  • Barnes CO; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
  • Schmidt F; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.
  • Schaefer-Babajew D; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • Lorenzi JCC; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • Flyak AI; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
  • DeLaitsch AT; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
  • Huey-Tubman KE; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.
  • Hou S; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
  • Schiffer CA; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • Gaebler C; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
  • Wang Z; Howard Hughes Medical Institute.
  • Da Silva J; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
  • Poston D; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
  • Finkin S; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • Cho A; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • Cipolla M; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.
  • Oliveira TY; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.
  • Millard KG; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • Ramos V; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • Gazumyan A; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • Rutkowska M; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • Caskey M; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • Nussenzweig MC; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • Bjorkman PJ; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • Hatziioannou T; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.
  • Bieniasz PD; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
bioRxiv ; 2021 Mar 08.
Article en En | MEDLINE | ID: mdl-33758864
ABSTRACT
Antibodies elicited in response to infection undergo somatic mutation in germinal centers that can result in higher affinity for the cognate antigen. To determine the effects of somatic mutation on the properties of SARS-CoV-2 spike receptor-binding domain (RBD)-specific antibodies, we analyzed six independent antibody lineages. As well as increased neutralization potency, antibody evolution changed pathways for acquisition of resistance and, in some cases, restricted the range of neutralization escape options. For some antibodies, maturation apparently imposed a requirement for multiple spike mutations to enable escape. For certain antibody lineages, maturation enabled neutralization of circulating SARS-CoV-2 variants of concern and heterologous sarbecoviruses. Antibody-antigen structures revealed that these properties resulted from substitutions that allowed additional variability at the interface with the RBD. These findings suggest that increasing antibody diversity through prolonged or repeated antigen exposure may improve protection against diversifying SARS-CoV-2 populations, and perhaps against other pandemic threat coronaviruses.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos