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.

Repeat vaccination with COVID-19 mRNA vaccines has been shown to increase breadth of the antibody response. Here the authors demonstrate that B cell clones induced by the ancestral COVID-19 vaccine develop into daughter clones with different reactivity to individual SARS-CoV-2 variants through the accumulation of somatic hypermutations.

Details

Title
An ancestral SARS-CoV-2 vaccine induces anti-Omicron variants antibodies by hypermutation
Author
Park, Seoryeong 1   VIAFID ORCID Logo  ; Choi, Jaewon 2 ; Lee, Yonghee 3 ; Noh, Jinsung 4 ; Kim, Namphil 3 ; Lee, JinAh 5   VIAFID ORCID Logo  ; Cho, Geummi 6   VIAFID ORCID Logo  ; Kim, Sujeong 6 ; Yoo, Duck Kyun 6   VIAFID ORCID Logo  ; Kang, Chang Kyung 7 ; Choe, Pyoeng Gyun 7 ; Kim, Nam Joong 7 ; Park, Wan Beom 7   VIAFID ORCID Logo  ; Kim, Seungtaek 5   VIAFID ORCID Logo  ; Oh, Myoung-don 7   VIAFID ORCID Logo  ; Kwon, Sunghoon 8   VIAFID ORCID Logo  ; Chung, Junho 9   VIAFID ORCID Logo 

1  Seoul National University College of Medicine, Department of Biochemistry and Molecular Biology, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University College of Medicine, Interdisciplinary Program in Cancer Biology Major, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
2  Seoul National University, Interdisciplinary Program in Bioengineering, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University, Integrated Major in Innovative Medical Science, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
3  Seoul National University, Department of Electrical and Computer Engineering, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
4  Seoul National University, Department of Electrical and Computer Engineering, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University, Bio-MAX Institute, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
5  Institut Pasteur Korea, Zoonotic Virus Laboratory, Seongnam, Republic of Korea (GRID:grid.418549.5) (ISNI:0000 0004 0494 4850) 
6  Seoul National University College of Medicine, Department of Biochemistry and Molecular Biology, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University College of Medicine, Department of Biomedical Sciences, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
7  Seoul National University College of Medicine, Department of Internal Medicine, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
8  Seoul National University, Interdisciplinary Program in Bioengineering, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University, Department of Electrical and Computer Engineering, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University, Bio-MAX Institute, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
9  Seoul National University College of Medicine, Department of Biochemistry and Molecular Biology, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University College of Medicine, Interdisciplinary Program in Cancer Biology Major, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University College of Medicine, Department of Biomedical Sciences, Seoul, Republic of Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
Pages
3368
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-024-47743-1
ProQuest document ID
3042231214
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.