biostudies-literatureUnknownKaku CINIAID NIH HHSNCI NIH HHSUnderstanding the evolution of antibody immunity following heterologous SAR-CoV-2 breakthrough infection will inform the development of next-generation vaccines. Here, we tracked SARS-CoV-2 receptor binding domain (RBD)-specific antibody responses up to six months following Omicron BA.1 breakthrough infection in mRNA-vaccinated individuals. Cross-reactive serum neutralizing antibody and memory B cell (MBC) responses declined by two- to four-fold through the study period. Breakthrough infection elicited minimal de novo Omicron-specific B cell responses but drove affinity maturation of pre-existing cross-reactive MBCs toward BA.1. Public clones dominated the neutralizing antibody response at both early and late time points, and their escape mutation profiles predicted newly emergent Omicron bioRxiv : the preprint server for biology2022.09.21.508922https://www.ebi.ac.uk/biostudies/studies/S-EPMC9516849biostudies-literatureEvolution of antibody immunity following Omicron BA.1 breakthrough infection.PMC9516849P30 CA023108UM1 AI144462K99 AI166250R01 AI141707Geoghegan JCZhou PWalker LMSong GStarr TNBurton DRBloom JDRaiees AKaku CIDugan HLKhalife PChampney ERMielcarz DWfalseEvolution of antibody immunity following Omicron BA.1 breakthrough infection.Understanding the evolution of antibody immunity following heterologous SAR-CoV-2 breakthrough infection will inform the development of next-generation vaccines. Here, we tracked SARS-CoV-2 receptor binding domain (RBD)-specific antibody responses up to six months following Omicron BA.1 breakthrough infection in mRNA-vaccinated individuals. Cross-reactive serum neutralizing antibody and memory B cell (MBC) responses declined by two- to four-fold through the study period. Breakthrough infection elicited minimal de novo Omicron-specific B cell responses but drove affinity maturation of pre-existing cross-reactive MBCs toward BA.1. Public clones dominated the neutralizing antibody response at both early and late time points, and their escape mutation profiles predicted newly emergent Omicron 2022-01-01T00:00:00Z2022 Sep2026-05-05T03:15:40.3Z2025-04-03T21:30:40.366ZS-EPMC95168493617212410.1101/2022.09.21.508922