B cell somatic hypermutation following COVID-19 vaccination with Ad26.COV2.S

Catherine Jacob-Dolan; Michelle Lifton; Olivia C. Powers; Jessica Miller; Nicole P. Hachmann; Mya Vu; Nehalee Surve; Camille R. Mazurek; Jana L. Fisher; Stefanie Rodrigues; Robert C. Patio; Trisha Anand; Mathieu Le Gars; Jerald Sadoff; Aaron G. Schmidt; Dan H. Barouch

iScience (May 2024)

B cell somatic hypermutation following COVID-19 vaccination with Ad26.COV2.S

Catherine Jacob-Dolan,
Michelle Lifton,
Olivia C. Powers,
Jessica Miller,
Nicole P. Hachmann,
Mya Vu,
Nehalee Surve,
Camille R. Mazurek,
Jana L. Fisher,
Stefanie Rodrigues,
Robert C. Patio,
Trisha Anand,
Mathieu Le Gars,
Jerald Sadoff,
Aaron G. Schmidt,
Dan H. Barouch

Affiliations

Catherine Jacob-Dolan: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA; Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA, USA; Harvard Medical School, Department of Microbiology, Boston, MA, USA; Harvard Medical School, Department of Immunology, Boston, MA, USA
Michelle Lifton: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA
Olivia C. Powers: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA
Jessica Miller: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA
Nicole P. Hachmann: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA
Mya Vu: Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA, USA
Nehalee Surve: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA
Camille R. Mazurek: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA
Jana L. Fisher: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA
Stefanie Rodrigues: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA
Robert C. Patio: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA
Trisha Anand: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA
Mathieu Le Gars: Janssen Vaccines and Prevention B.V., Leiden, the Netherlands
Jerald Sadoff: Janssen Vaccines and Prevention B.V., Leiden, the Netherlands
Aaron G. Schmidt: Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA, USA; Harvard Medical School, Department of Microbiology, Boston, MA, USA
Dan H. Barouch: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA; Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA, USA; Harvard Medical School, Department of Immunology, Boston, MA, USA; Corresponding author

Journal volume & issue: Vol. 27, no. 5
p. 109716

Abstract

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Summary: The viral vector-based COVID-19 vaccine Ad26.COV2.S has been recommended by the WHO since 2021 and has been administered to over 200 million people. Prior studies have shown that Ad26.COV2.S induces durable neutralizing antibodies (NAbs) that increase in coverage of variants over time, even in the absence of boosting or infection. Here, we studied humoral responses following Ad26.COV2.S vaccination in individuals enrolled in the initial Phase 1/2a trial of Ad26.COV2.S in 2020. Through 8 months post vaccination, serum NAb responses increased to variants, including B.1.351 (Beta) and B.1.617.2 (Delta), without additional boosting or infection. The level of somatic hypermutation, measured by nucleotide changes in the VDJ region of the heavy and light antibody chains, increased in Spike-specific B cells. Highly mutated mAbs from these sequences neutralized more SARS-CoV-2 variants than less mutated comparators. These findings suggest that the increase in NAb breadth over time following Ad26.COV2.S vaccination is mediated by affinity maturation.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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