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Affinity maturation of SARS-CoV-2 neutralizing antibodies confers potency, breadth, and resilience to viral escape mutations.
Muecksch, Frauke; Weisblum, Yiska; Barnes, Christopher O; Schmidt, Fabian; Schaefer-Babajew, Dennis; Wang, Zijun; C Lorenzi, Julio C; Flyak, Andrew I; DeLaitsch, Andrew T; Huey-Tubman, Kathryn E; Hou, Shurong; Schiffer, Celia A; Gaebler, Christian; 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.
  • 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.
  • Wang Z; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • C Lorenzi JC; 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; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Hou S; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
  • Schiffer CA; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
  • Gaebler C; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • Da Silva J; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA.
  • Poston D; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, 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 Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • Oliveira TY; Laboratory of Molecular Immunology, 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 Retrovirology, 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; Howard Hughes Medical Institute. Electronic address: nussen@mail.rockefeller.edu.
  • Bjorkman PJ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: bjorkman@caltech.edu.
  • Hatziioannou T; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA. Electronic address: thatziio@rockefeller.edu.
  • Bieniasz PD; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute. Electronic address: pbieniasz@rockefeller.edu.
Immunity ; 54(8): 1853-1868.e7, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1330891
ABSTRACT
Antibodies elicited by infection accumulate somatic mutations in germinal centers that can increase affinity for cognate antigens. We analyzed 6 independent groups of clonally related severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) Spike receptor-binding domain (RBD)-specific antibodies from 5 individuals shortly after infection and later in convalescence to determine the impact of maturation over months. In addition to increased affinity and neutralization potency, antibody evolution changed the mutational pathways for the acquisition of viral resistance and restricted neutralization escape options. For some antibodies, maturation imposed a requirement for multiple substitutions to enable escape. For certain antibodies, affinity maturation enabled the 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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Host-Pathogen Interactions / SARS-CoV-2 / COVID-19 / Antibody Affinity / Mutation Type of study: Prognostic study / Randomized controlled trials Topics: Variants Limits: Humans Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: J.immuni.2021.07.008

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Host-Pathogen Interactions / SARS-CoV-2 / COVID-19 / Antibody Affinity / Mutation Type of study: Prognostic study / Randomized controlled trials Topics: Variants Limits: Humans Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: J.immuni.2021.07.008