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
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.
