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, Junho Chung, Sunghoon Kwon, 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.