{"doi":"10.1101/2022.09.22.509040","title":"SARS-CoV-2 Omicron boosting induces de novo B cell response in humans","abstract":"Abstract The primary two-dose SARS-CoV-2 mRNA vaccine series are strongly immunogenic in humans, but the emergence of highly infectious variants necessitated additional doses of these vaccines and the development of new variant-derived ones 1–4 . SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells (MBCs) 5–9 . It remains unclear, however, whether the additional doses induce germinal centre (GC) reactions where reengaged B cells can further mature and whether variant-derived vaccines can elicit responses to novel epitopes specific to such variants. Here, we show that boosting with the original SARS- CoV-2 spike vaccine (mRNA-1273) or a B.1.351/B.1.617.2 (Beta/Delta) bivalent vaccine (mRNA-1273.213) induces robust spike-specific GC B cell responses in humans. The GC response persisted for at least eight weeks, leading to significantly more mutated antigen-specific MBC and bone marrow plasma cell compartments. Interrogation of MBC-derived spike-binding monoclonal antibodies (mAbs) isolated from individuals boosted with either mRNA-1273, mRNA-1273.213, or a monovalent Omicron BA.1-based vaccine (mRNA-1273.529) revealed a striking imprinting effect by the primary vaccination series, with all mAbs (n=769) recognizing the original SARS-CoV-2 spike protein. Nonetheless, using a more targeted approach, we isolated mAbs that recognized the spike protein of the SARS-CoV-2 Omicron (BA.1) but not the original SARS-CoV-2 spike from the mRNA-1273.529 boosted individuals. The latter mAbs were less mutated and recognized novel epitopes within the spike protein, suggesting a naïve B cell origin. Thus, SARS-CoV-2 boosting in humans induce robust GC B cell responses, and immunization with an antigenically distant spike can overcome the antigenic imprinting by the primary vaccination series.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":296450,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9554,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":439801,"name":"Sameer Kumar Malladi","orcid":"0000-0001-5131-4518","position":1,"is_corresponding":false},{"id":242710,"name":"Julian Q. Zhou","orcid":"0000-0001-9602-2092","position":2,"is_corresponding":false},{"id":106714,"name":"Zhuoming Liu","orcid":"0000-0001-8198-0976","position":3,"is_corresponding":false},{"id":408059,"name":"Baoling Ying","orcid":null,"position":4,"is_corresponding":false},{"id":614787,"name":"Wooseob Kim","orcid":"0000-0002-9199-1000","position":5,"is_corresponding":false},{"id":225533,"name":"Aaron J. Schmitz","orcid":"0000-0002-8077-6751","position":6,"is_corresponding":false},{"id":55451,"name":"Tingting Lei","orcid":"0000-0002-8592-4178","position":7,"is_corresponding":false},{"id":805454,"name":"Stephen Horváth","orcid":"0000-0001-5324-1666","position":8,"is_corresponding":false},{"id":271034,"name":"Alexandria J. Sturtz","orcid":"0000-0001-6548-5086","position":9,"is_corresponding":false},{"id":242711,"name":"Katherine M. McIntire","orcid":"0000-0002-6262-4260","position":10,"is_corresponding":false},{"id":983806,"name":"Birk Evavold","orcid":null,"position":11,"is_corresponding":false},{"id":983807,"name":"Fangjie Han","orcid":null,"position":12,"is_corresponding":false},{"id":689736,"name":"Suzanne M. Scheaffer","orcid":"0009-0001-0459-0816","position":13,"is_corresponding":false},{"id":983808,"name":"Isabella F. Fox","orcid":null,"position":14,"is_corresponding":false},{"id":805455,"name":"Luis Parra-Rodriguez","orcid":"0000-0003-1746-0743","position":15,"is_corresponding":false},{"id":123992,"name":"Raffael Nachbagauer","orcid":"0000-0001-5568-5420","position":16,"is_corresponding":false},{"id":983809,"name":"Biliana Nestorova","orcid":null,"position":17,"is_corresponding":false},{"id":838767,"name":"Spyros Chalkias","orcid":"0000-0002-6254-1158","position":18,"is_corresponding":false},{"id":555572,"name":"Christopher W Farnsworth","orcid":"0000-0001-7169-3850","position":19,"is_corresponding":false},{"id":12097,"name":"Michael K. Klebert","orcid":"0000-0003-3329-3674","position":20,"is_corresponding":false},{"id":260042,"name":"Iskra Pusic","orcid":"0000-0003-1725-5184","position":21,"is_corresponding":false},{"id":983243,"name":"Benjamin S. Strnad","orcid":"0000-0003-2308-1299","position":22,"is_corresponding":false},{"id":285661,"name":"William D. Middleton","orcid":"0000-0002-9869-1107","position":23,"is_corresponding":false},{"id":285660,"name":"Sharlene A. Teefey","orcid":"0000-0002-3832-6781","position":24,"is_corresponding":false},{"id":103752,"name":"Sean P. J. Whelan","orcid":"0000-0003-1564-8590","position":25,"is_corresponding":false},{"id":106529,"name":"Michael Diamond","orcid":"0000-0002-8791-3165","position":26,"is_corresponding":false},{"id":593255,"name":"Robert Paris","orcid":"0000-0003-3234-5989","position":27,"is_corresponding":false},{"id":259653,"name":"Jane A. O’Halloran","orcid":"0000-0001-8265-9471","position":28,"is_corresponding":false},{"id":552303,"name":"Rachel M. Presti","orcid":"0000-0002-5469-0727","position":29,"is_corresponding":false},{"id":225532,"name":"Jackson S. Turner","orcid":"0000-0002-4396-6265","position":30,"is_corresponding":false},{"id":225537,"name":"Ali H. Ellebedy","orcid":"0000-0002-6129-2532","position":31,"is_corresponding":false},{"id":225531,"name":"Wafaa B. Alsoussi","orcid":"0000-0002-5805-4461","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T00:31:16.555318Z","pmid":"36172127","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}