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Updated: Jun 28, 2025

Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches
Published on: April 20, 2021
B cell somatic hypermutation following COVID-19 vaccination with Ad26.COV2.S
Catherine Jacob-Dolan1,2,3,4, Michelle Lifton1, Olivia C Powers1
1Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Abstract:
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.
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