Convergent antibody responses to the SARS-CoV-2 spike protein in convalescent and vaccinated individuals

Elaine C Chen; Pavlo Gilchuk; Seth J Zost; Naveenchandra Suryadevara; Emma S Winkler; Carly R Cabel; Elad Binshtein; Rita E Chen; Rachel E Sutton; Jessica Rodriguez; Samuel Day; Luke Myers; Andrew Trivette; Jazmean K Williams; Edgar Davidson; Shuaizhi Li; Benjamin J Doranz; Samuel K Campos; Robert H Carnahan; Curtis A Thorne; Michael S Diamond; James E Crowe Jr

doi:10.1016/j.celrep.2021.109604

Convergent antibody responses to the SARS-CoV-2 spike protein in convalescent and vaccinated individuals

Cell Rep. 2021 Aug 24;36(8):109604. doi: 10.1016/j.celrep.2021.109604. Epub 2021 Aug 10.

Authors

Elaine C Chen¹, Pavlo Gilchuk², Seth J Zost², Naveenchandra Suryadevara², Emma S Winkler³, Carly R Cabel⁴, Elad Binshtein², Rita E Chen³, Rachel E Sutton², Jessica Rodriguez², Samuel Day², Luke Myers², Andrew Trivette², Jazmean K Williams⁵, Edgar Davidson⁵, Shuaizhi Li⁶, Benjamin J Doranz⁵, Samuel K Campos⁷, Robert H Carnahan², Curtis A Thorne⁴, Michael S Diamond⁸, James E Crowe Jr⁹

Affiliations

¹ Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
² Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
³ Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA.
⁴ Department of Cellular & Molecular Medicine, University of Arizona College of Medicine, Tucson, AZ 85724, USA; Cancer Biology Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ 85724, USA.
⁵ Integral Molecular, Inc., Philadelphia, PA 19104, USA.
⁶ Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ 85724, USA.
⁷ Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ 85724, USA; Cancer Biology Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ 85724, USA.
⁸ Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
⁹ Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: [email protected].

Abstract

Unrelated individuals can produce genetically similar clones of antibodies, known as public clonotypes, which have been seen in responses to different infectious diseases, as well as healthy individuals. Here we identify 37 public clonotypes in memory B cells from convalescent survivors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or in plasmablasts from an individual after vaccination with mRNA-encoded spike protein. We identify 29 public clonotypes, including clones recognizing the receptor-binding domain (RBD) in the spike protein S1 subunit (including a neutralizing, angiotensin-converting enzyme 2 [ACE2]-blocking clone that protects in vivo) and others recognizing non-RBD epitopes that bind the S2 domain. Germline-revertant forms of some public clonotypes bind efficiently to spike protein, suggesting these common germline-encoded antibodies are preconfigured for avid recognition. Identification of large numbers of public clonotypes provides insight into the molecular basis of efficacy of SARS-CoV-2 vaccines and sheds light on the immune pressures driving the selection of common viral escape mutants.

Keywords: COVID-19; SARS-CoV; SARS-CoV-2; adaptive immunity; antibodies; coronavirus; human; monoclonal; public clonotypes; vaccines.

Abstract

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