An ancestral SARS-CoV-2 vaccine induces anti-Omicron variants antibodies by hypermutation

Seoryeong Park, Jaewon Choi, Yonghee Lee, Jinsung Noh, Namphil Kim, JinAh Lee, Geummi Cho, Sujeong Kim, Duck Kyun Yoo, Chang Kyung Kang, Pyoeng Gyun Choe, Nam Joong Kim, Wan Beom Park, Seungtaek Kim (), Myoung-don Oh (), Sunghoon Kwon () and Junho Chung ()
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Seoryeong Park: Seoul National University College of Medicine
Jaewon Choi: Seoul National University
Yonghee Lee: Seoul National University
Jinsung Noh: Seoul National University
Namphil Kim: Seoul National University
JinAh Lee: Institut Pasteur Korea
Geummi Cho: Seoul National University College of Medicine
Sujeong Kim: Seoul National University College of Medicine
Duck Kyun Yoo: Seoul National University College of Medicine
Chang Kyung Kang: Seoul National University College of Medicine
Pyoeng Gyun Choe: Seoul National University College of Medicine
Nam Joong Kim: Seoul National University College of Medicine
Wan Beom Park: Seoul National University College of Medicine
Seungtaek Kim: Institut Pasteur Korea
Myoung-don Oh: Seoul National University College of Medicine
Sunghoon Kwon: Seoul National University
Junho Chung: Seoul National University College of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-9

Abstract: Abstract The immune escape of Omicron variants significantly subsides by the third dose of an mRNA vaccine. However, it is unclear how Omicron variant-neutralizing antibodies develop under repeated vaccination. We analyze blood samples from 41 BNT162b2 vaccinees following the course of three injections and analyze their B-cell receptor (BCR) repertoires at six time points in total. The concomitant reactivity to both ancestral and Omicron receptor-binding domain (RBD) is achieved by a limited number of BCR clonotypes depending on the accumulation of somatic hypermutation (SHM) after the third dose. Our findings suggest that SHM accumulation in the BCR space to broaden its specificity for unseen antigens is a counterprotective mechanism against virus variant immune escape.

Date: 2024
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DOI: 10.1038/s41467-024-47743-1

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