Omicron BA.1 breakthrough infection in vaccinated individuals recall memory B cells to confer immunity

By Neha MathurSep 26 2022Reviewed by Aimee Molineux In a recent study posted to the bioRxiv* server, a team of researchers followed up with individuals vaccinated with a coronavirus disease 2019 vaccine based on the messenger ribonucleic acid platform up to six months following Omicron BA.1 breakthrough infection to trace the evolution of their antibody immunity.

About the study In the present study, researchers created a cohort comprising seven mRNA-1273 vaccinated donors to profile their SARS-CoV-2-specific serological and memory B responses up to six months following Omicron BA.1 breakthrough infection. Initially, they characterized their antibody response for 14 to 27 days after BA.1 breakthrough infection.

From 363 natively paired full-length immunoglobulins G , they randomly selected one to two antibodies belonging to each convergent germline to perform deep mutational scanning analysis. This screening involved a library encoding all possible amino acid substitutions from BA.1. These analyses helped the researchers compare the molecular characteristics of antibodies isolated at early and late periods points following BA. 1 infection.

Total RBD reactive B cells and WT/BA.1 cross-reactive B cells comprised a median of 0.44% and 0.37% of class-switched IgG+ or IgA+ B cells, respectively, at five to six months time points. Thus, 86% of these B cells displayed BA.1/WT cross-reactivity, compared with 75% at one month post-infection. WT-specific B cells decreased from 25% to 11% between one and five to six months-timepoint.

These antibodies displayed 1.7-fold improved binding to BA.1 and two-fold reduced binding affinity to the WT RBD relative to early antibodies, indicating affinity maturation towards BA.1 at the expense of WT affinity. These late antibodies showed more balanced affinity profiles than the early antibodies . Notably, convergent nAb classes dominated the BA.1 breakthrough response at early and late time points.

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