{"doi":"10.1084/jem.20251146","title":"Common cold embecovirus imprinting primes broadly neutralizing antibody responses to SARS-CoV-2 S2","abstract":"The S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike is highly conserved across coronavirus strains and therefore is a potential pan-coronavirus vaccine target. However, antibodies targeting this region are typically non-neutralizing. We report herein that S2-targeting antibodies from patients who recovered from SARS-CoV-2 infection bound only closely related sarbecovirus subgenus strains and, like most known S2 antibodies, none of these were neutralizing. In contrast, first-exposure, severe acutely infected COVID-19 patients predominantly induced back-boosted antibody-secreting cells imprinted against past common cold coronavirus strain OC43 that were cross-reactive to as many as five subgenera of betacoronavirus strains and gave rise to antibodies that were neutralizing and protective. The antibodies targeted two different sites: one defined by competition with stem helix antibodies, and the second to an underdescribed epitope at the apex of S2. These findings suggest that S2-targeted vaccines could strategically exploit controlled OC43 priming followed by SARS-CoV-2 boosting to enhance the breadth and quality of protective antibody responses.","journal":"The Journal of Experimental Medicine","year":2025,"id":515262,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":641903,"name":"Atsuhiro Yasuhara","orcid":"0000-0002-7781-0197","position":1,"is_corresponding":false},{"id":1379479,"name":"Suncheol Park","orcid":"0000-0003-3910-6454","position":2,"is_corresponding":false},{"id":230740,"name":"Sandhya Bangaru","orcid":"0000-0001-7994-4693","position":3,"is_corresponding":false},{"id":284391,"name":"Lei Li","orcid":"0000-0002-8828-5199","position":4,"is_corresponding":false},{"id":1299031,"name":"Chloe Troxell","orcid":"0009-0003-9647-324X","position":5,"is_corresponding":false},{"id":107104,"name":"Peter Halfmann","orcid":"0000-0002-1648-1625","position":6,"is_corresponding":false},{"id":628433,"name":"Steven A. 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