Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike

Pei Tong; Avneesh Gautam; Ian W Windsor; Meghan Travers; Yuezhou Chen; Nicholas Garcia; Noah B Whiteman; Lindsay G A McKay; Nadia Storm; Lauren E Malsick; Anna N Honko; Felipe J N Lelis; Shaghayegh Habibi; Simon Jenni; Yongfei Cai; Linda J Rennick; W Paul Duprex; Kevin R McCarthy; Christy L Lavine; Teng Zuo; Junrui Lin; Adam Zuiani; Jared Feldman; Elizabeth A MacDonald; Blake M Hauser; Anthony Griffths; Michael S Seaman; Aaron G Schmidt; Bing Chen; Donna Neuberg; Goran Bajic; Stephen C Harrison; Duane R Wesemann

doi:10.1016/j.cell.2021.07.025

Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike

Cell. 2021 Sep 16;184(19):4969-4980.e15. doi: 10.1016/j.cell.2021.07.025. Epub 2021 Jul 23.

Authors

Pei Tong¹, Avneesh Gautam¹, Ian W Windsor², Meghan Travers¹, Yuezhou Chen¹, Nicholas Garcia¹, Noah B Whiteman¹, Lindsay G A McKay³, Nadia Storm³, Lauren E Malsick³, Anna N Honko³, Felipe J N Lelis¹, Shaghayegh Habibi¹, Simon Jenni⁴, Yongfei Cai⁵, Linda J Rennick⁶, W Paul Duprex⁶, Kevin R McCarthy⁶, Christy L Lavine⁷, Teng Zuo¹, Junrui Lin¹, Adam Zuiani¹, Jared Feldman⁸, Elizabeth A MacDonald⁴, Blake M Hauser⁸, Anthony Griffths³, Michael S Seaman⁷, Aaron G Schmidt⁹, Bing Chen¹⁰, Donna Neuberg¹¹, Goran Bajic¹², Stephen C Harrison¹³, Duane R Wesemann¹⁴

Affiliations

¹ Department of Medicine, Division of Allergy and Immunology, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
² Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Laboratory of Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
³ Department of Microbiology, Boston University School of Medicine, Boston, MA 02115, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02115, USA.
⁴ Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
⁵ Laboratory of Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
⁶ The Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; The Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
⁷ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
⁸ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
⁹ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Massachusetts Consortium on Pathogen Readiness, Boston, MA 02115, USA.
¹⁰ Laboratory of Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Massachusetts Consortium on Pathogen Readiness, Boston, MA 02115, USA.
¹¹ Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
¹² Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Laboratory of Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
¹³ Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Laboratory of Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Massachusetts Consortium on Pathogen Readiness, Boston, MA 02115, USA; Howard Hughes Medical Institute, Boston, MA 02115, USA.
¹⁴ Department of Medicine, Division of Allergy and Immunology, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Massachusetts Consortium on Pathogen Readiness, Boston, MA 02115, USA. Electronic address: [email protected].

Abstract

Memory B cell reserves can generate protective antibodies against repeated SARS-CoV-2 infections, but with unknown reach from original infection to antigenically drifted variants. We charted memory B cell receptor-encoded antibodies from 19 COVID-19 convalescent subjects against SARS-CoV-2 spike (S) and found seven major antibody competition groups against epitopes recurrently targeted across individuals. Inclusion of published and newly determined structures of antibody-S complexes identified corresponding epitopic regions. Group assignment correlated with cross-CoV-reactivity breadth, neutralization potency, and convergent antibody signatures. Although emerging SARS-CoV-2 variants of concern escaped binding by many members of the groups associated with the most potent neutralizing activity, some antibodies in each of those groups retained affinity-suggesting that otherwise redundant components of a primary immune response are important for durable protection from evolving pathogens. Our results furnish a global atlas of S-specific memory B cell repertoires and illustrate properties driving viral escape and conferring robustness against emerging variants.

Keywords: B cell; COVID-19; SARS-CoV-2; antibody; breadth; cross-reactivity; memory; neutralization; repertoire; variants.

Abstract

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