biostudies-literatureWang ZNational Center for Advancing Translational SciencesNCATS NIH HHSHoward Hughes Medical InstituteNIAID NIH HHSNational Institutes of HealthRockefeller Universitye20221006https://www.ebi.ac.uk/biostudies/studies/S-EPMC9513381biostudies-literatureUnknown219(12)Individuals who receive a third mRNA vaccine dose show enhanced protection against severe COVID-19, but little is known about the impact of breakthrough infections on memory responses. Here, we examine the memory antibodies that develop after a third or fourth antigenic exposure by Delta or Omicron BA.1 infection, respectively. A third exposure to antigen by Delta breakthrough increases the number of memory B cells that produce antibodies with comparable potency and breadth to a third mRNA vaccine dose. A fourth antigenic exposure with Omicron BA.1 infection increased variant-specific plasma antibody and memory B cell responses. However, the fourth exposure did not increase the overall frequency of memory B cells or their general potency or breadth compared to a third mRNA vaccine dose. InThe Journal of experimental medicineMemory B cell responses to Omicron subvariants after SARS-CoV-2 mRNA breakthrough infection in humans.PMC9513381P01 AI165075U19 AI111825P01 AI138938R37-AI64003P01-AI138398-S1R01AI78788UL1 TR001866R01 AI0787882U19AI111825R37 AI064003P01AI165075Canis MKaczynska ABen Tanfous TDizon JGazumyan ANussenzweig MCMillard KGSchmidt FCho ACaskey MMuecksch FDa Silva JJohnson BWitte LWang ZShimeliovich IBednarski ERamos VZong SHatziioannou TZhou PRaspe RTurroja MOliveira TYBieniasz PDGaebler CJankovic MYao KHfalseMemory B cell responses to Omicron subvariants after SARS-CoV-2 mRNA breakthrough infection in humans.Individuals who receive a third mRNA vaccine dose show enhanced protection against severe COVID-19, but little is known about the impact of breakthrough infections on memory responses. Here, we examine the memory antibodies that develop after a third or fourth antigenic exposure by Delta or Omicron BA.1 infection, respectively. A third exposure to antigen by Delta breakthrough increases the number of memory B cells that produce antibodies with comparable potency and breadth to a third mRNA vaccine dose. A fourth antigenic exposure with Omicron BA.1 infection increased variant-specific plasma antibody and memory B cell responses. However, the fourth exposure did not increase the overall frequency of memory B cells or their general potency or breadth compared to a third mRNA vaccine dose. In2022-01-01T00:00:00Z2022 Dec2026-04-08T11:57:56.319Z2024-11-12T00:22:50.359ZS-EPMC95133813614939810.1084/jem.20221006