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Nat. Commun., Apr 20 2024, 15 (1) | https://doi.org/10.1038/s41467-024-47743-1 An ancestral SARS-CoV-2 vaccine induces anti-Omicron variants antibodies by hypermutation

Seoryeong Park ^1,2,10, Jaewon Choi ^3,4,10, Yonghee Lee ⁵, Jinsung Noh ^5,6, Namphil Kim ⁵, JinAh Lee ⁷, Geummi Cho ^1,8, Sujeong Kim ^1,8, Duck Kyun Yoo ^1,8, Chang Kyung Kang ⁹, Pyoeng Gyun Choe ⁹, Nam Joong Kim ⁹, Wan Beom Park ⁹, Seungtaek Kim ^7,*, Myoung-don Oh ^9,*, Sunghoon Kwon ^3,5,6,* & Junho Chung ^1,2,8,*

¹Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Republic of Korea.
²Interdisciplinary Program in Cancer Biology Major, Seoul National University College of Medicine, Seoul, Republic of Korea.
³Interdisciplinary Program in Bioengineering, Seoul National University, Seoul, Republic of Korea.
⁴Integrated Major in Innovative Medical Science, Seoul National University, Seoul, Republic of Korea.
⁵Department of Electrical and Computer Engineering, Seoul National University, Seoul, Republic of Korea.
⁶Bio-MAX Institute, Seoul National University, Seoul, Republic of Korea.
⁷Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam, Republic of Korea.
⁸Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁹Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
¹⁰These authors contributed equally: Seoryeong Park, Jaewon Choi.

^*Corresponding authors: correspondence to Seungtaek Kim, Myoung-don Oh, Sunghoon Kwon or Junho Chung

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.

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형식Research article
게재일2024년 04월 (BRIC 등록일 2024-04-22)
연구진국내 연구진
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