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

Seoryeong Park; Jaewon Choi; Yonghee Lee; Jinsung Noh; Namphil Kim; Jin Ah 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; Junho Chung

doi:10.1038/s41467-024-47743-1

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

Seoryeong Park, Jaewon Choi, Yonghee Lee, Jinsung Noh, Namphil Kim, Jin Ah 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, Junho Chung

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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.

Original language	English
Article number	3368
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-47743-1
State	Published - Dec 2024

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© The Author(s) 2024.

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title = "An ancestral SARS-CoV-2 vaccine induces anti-Omicron variants antibodies by hypermutation",

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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AU - Park, Seoryeong

AU - Choi, Jaewon

AU - Lee, Yonghee

AU - Noh, Jinsung

AU - Kim, Namphil

AU - Lee, Jin Ah

AU - Cho, Geummi

AU - Kim, Sujeong

AU - Yoo, Duck Kyun

AU - Kang, Chang Kyung

AU - Choe, Pyoeng Gyun

AU - Kim, Nam Joong

AU - Park, Wan Beom

AU - Kim, Seungtaek

AU - Oh, Myoung Don

AU - Kwon, Sunghoon

AU - Chung, Junho

PY - 2024/12

Y1 - 2024/12

N2 - 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.

AB - 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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SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

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M1 - 3368

ER -

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

Abstract

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