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B cell genomics behind cross-neutralization of SARS-CoV-2 variants and SARS-CoV.
Scheid, Johannes F; Barnes, Christopher O; Eraslan, Basak; Hudak, Andrew; Keeffe, Jennifer R; Cosimi, Lisa A; Brown, Eric M; Muecksch, Frauke; Weisblum, Yiska; Zhang, Shuting; Delorey, Toni; Woolley, Ann E; Ghantous, Fadi; Park, Sung-Moo; Phillips, Devan; Tusi, Betsabeh; Huey-Tubman, Kathryn E; Cohen, Alexander A; Gnanapragasam, Priyanthi N P; Rzasa, Kara; Hatziioanno, Theodora; Durney, Michael A; Gu, Xiebin; Tada, Takuya; Landau, Nathaniel R; West, Anthony P; Rozenblatt-Rosen, Orit; Seaman, Michael S; Baden, Lindsey R; Graham, Daniel B; Deguine, Jacques; Bieniasz, Paul D; Regev, Aviv; Hung, Deborah; Bjorkman, Pamela J; Xavier, Ramnik J.
Afiliação
  • Scheid JF; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospi
  • Barnes CO; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Eraslan B; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
  • Hudak A; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
  • Keeffe JR; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Cosimi LA; Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Brown EM; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Muecksch F; Laboratory of Molecular Virology, The Rockefeller University, New York, NY 10065, USA.
  • Weisblum Y; Laboratory of Molecular Virology, The Rockefeller University, New York, NY 10065, USA.
  • Zhang S; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
  • Delorey T; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Woolley AE; Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Ghantous F; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
  • Park SM; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
  • Phillips D; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Tusi B; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
  • Huey-Tubman KE; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Cohen AA; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Gnanapragasam PNP; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Rzasa K; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
  • Hatziioanno T; Laboratory of Molecular Virology, The Rockefeller University, New York, NY 10065, USA.
  • Durney MA; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
  • Gu X; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
  • Tada T; Department of Microbiology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • Landau NR; Department of Microbiology, NYU Grossman School of Medicine, New York, NY 10016, USA.
  • West AP; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Rozenblatt-Rosen O; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Seaman MS; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
  • Baden LR; Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Graham DB; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Deguine J; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
  • Bieniasz PD; Laboratory of Molecular Virology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
  • Regev A; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
  • Hung D; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Ho
  • Bjorkman PJ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: bjorkman@caltech.edu.
  • Xavier RJ; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospi
Cell ; 184(12): 3205-3221.e24, 2021 06 10.
Article em En | MEDLINE | ID: mdl-34015271
Monoclonal antibodies (mAbs) are a focus in vaccine and therapeutic design to counteract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. Here, we combined B cell sorting with single-cell VDJ and RNA sequencing (RNA-seq) and mAb structures to characterize B cell responses against SARS-CoV-2. We show that the SARS-CoV-2-specific B cell repertoire consists of transcriptionally distinct B cell populations with cells producing potently neutralizing antibodies (nAbs) localized in two clusters that resemble memory and activated B cells. Cryo-electron microscopy structures of selected nAbs from these two clusters complexed with SARS-CoV-2 spike trimers show recognition of various receptor-binding domain (RBD) epitopes. One of these mAbs, BG10-19, locks the spike trimer in a closed conformation to potently neutralize SARS-CoV-2, the recently arising mutants B.1.1.7 and B.1.351, and SARS-CoV and cross-reacts with heterologous RBDs. Together, our results characterize transcriptional differences among SARS-CoV-2-specific B cells and uncover cross-neutralizing Ab targets that will inform immunogen and therapeutic design against coronaviruses.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Linfócitos B / Anticorpos Neutralizantes / Glicoproteína da Espícula de Coronavírus / SARS-CoV-2 Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Linfócitos B / Anticorpos Neutralizantes / Glicoproteína da Espícula de Coronavírus / SARS-CoV-2 Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2021 Tipo de documento: Article