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Recall of preexisting cross-reactive B cell memory after Omicron BA.1 breakthrough infection
United States.
Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, United States; Department of Microbiology and Immunology, Dartmouth College, Hanover, United States.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.ORCID iD: 0000-0003-2018-8592
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
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2022 (English)In: Science immunology, E-ISSN 2470-9468, Vol. 7, no 73, article id eabq3511Article in journal (Refereed) Published
Abstract [en]

Understanding immune responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection will facilitate the development of next-generation vaccines. Here, we profiled spike (S)-specific B cell responses after Omicron/BA.1 infection in messenger RNA-vaccinated donors. The acute antibody response was characterized by high levels of somatic hypermutation and a bias toward recognition of ancestral SARS-CoV-2 strains, suggesting the early activation of vaccine-induced memory B cells. BA.1 breakthrough infection induced a shift in B cell immunodominance hierarchy from the S2 subunit, which is highly conserved across SARS-CoV-2 variants of concern (VOCs), and toward the antigenically variable receptor binding domain (RBD). A large proportion of RBD-directed neutralizing antibodies isolated from BA.1 breakthrough infection donors displayed convergent sequence features and broadly recognized SARS-CoV-2 VOCs. Together, these findings provide insights into the role of preexisting immunity in shaping the B cell response to heterologous SARS-CoV-2 variant exposure.

Place, publisher, year, edition, pages
American Association for the Advancement of Science , 2022. Vol. 7, no 73, article id eabq3511
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Immunology in the medical area Infectious Medicine
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URN: urn:nbn:se:umu:diva-203211DOI: 10.1126/sciimmunol.abq3511ISI: 000852639600009PubMedID: 35549299Scopus ID: 2-s2.0-85134873054OAI: oai:DiVA.org:umu-203211DiVA, id: diva2:1728525
Available from: 2023-01-18 Created: 2023-01-18 Last updated: 2023-01-18Bibliographically approved

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Ahlm, ClasNormark, JohanForsell, Mattias N. E.

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