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

The immune escape of Omicron variants significantly subsides by the third dose of an mRNA vaccine, but how Omicron-neutralizing antibodies develop with repeated vaccination is unclear. We analyzed blood samples from 41 BNT162b2 vaccinees across three injections at six time points and profiled their B-cell receptor (BCR) repertoires. Combinatorial reactivity to both Omicron and ancestral receptor-binding domains (RBDs) was achieved by a limited number of BCR clonotypes, dependent on the accumulation of somatic hypermutation (SHM) after the third dose. These findings suggest that broadening of BCR specificity through SHM provides a counterprotective mechanism against immune escape by SARS-CoV-2 variants.

Seoryeong Park, Jaewon Choi, Yonghee Lee, Jinsung Noh, Namphil Kim, JinAh Lee, Geummi Cho, Sujeong Kim, Duck Kyun Yoo, Chang Kyung Kang, Pyeong Gyun Cho, Nam Joong Kim, Wan Beom Park, Seungtake Kim, Myoung-ong Oh, Sunghoon Kwon, Junho Chung