{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T23:47:11Z","timestamp":1785541631497,"version":"3.56.0"},"reference-count":47,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"publisher","award":["2022YFC2604100"],"award-info":[{"award-number":["2022YFC2604100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"publisher","award":["2042025kf0064"],"award-info":[{"award-number":["2042025kf0064"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"publisher","award":["32188101"],"award-info":[{"award-number":["32188101"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2022YFC2604100"],"award-info":[{"award-number":["2022YFC2604100"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2042025kf0064"],"award-info":[{"award-number":["2042025kf0064"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["32188101"],"award-info":[{"award-number":["32188101"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2022YFC2604100"],"award-info":[{"award-number":["2022YFC2604100"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2042025kf0064"],"award-info":[{"award-number":["2042025kf0064"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32188101"],"award-info":[{"award-number":["32188101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The COVID-19 pandemic, driven by SARS-CoV-2, continues to challenge global health due to emerging variants and the potential risk posed by related sarbecoviruses. Neutralizing antibodies targeting the spike (S) glycoprotein, particularly the receptor-binding domain (RBD), play a crucial role in viral neutralization and vaccine design. Although broadly neutralizing anti-RBD antibodies have been identified, the nature of cross-reactive humoral responses induced by natural infection with ancestral SARS-CoV-2 strains remains incompletely understood. Here, we isolated 105 S-specific monoclonal antibodies (mAbs) from individuals recovered from prototype SARS-CoV-2 infection. Of these, 30 mAbs cross-recognized SARS-CoV-1, including 25 RBD-directed mAbs, of which 12 displayed cross-neutralizing activity against both viruses. Among them, mAb 12C2 potently neutralized SARS-CoV-1 and multiple SARS-CoV-2 variants, likely through mechanisms that include inhibition of membrane fusion and potential destabilization of the S trimer. Cryo-electron microscopy revealed that 12C2 engages the outer face of the RBD, overlapping with the epitope recognized by the broadly neutralizing antibody S309 derived from SARS-CoV-1 convalescent. Collectively, these findings demonstrate that ancestral SARS-CoV-2 infection can elicit robust cross-neutralizing antibody responses and provide valuable insights for the design of broadly protective antibodies and vaccines.<\/jats:p>","DOI":"10.3390\/v17101285","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T08:09:42Z","timestamp":1758614982000},"page":"1285","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Broadly Sarbecovirus-Neutralizing Antibodies Induced by Ancestral SARS-CoV-2 Infection"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7526-0608","authenticated-orcid":false,"given":"Yiwei","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Animal Biosafety Level-III Laboratory\/Institute for Vaccine Research, Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyang","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3481-857X","authenticated-orcid":false,"given":"Xianying","family":"Chen","sequence":"additional","affiliation":[{"name":"Animal Biosafety Level-III Laboratory\/Institute for Vaccine Research, Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangyu","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5034-0269","authenticated-orcid":false,"given":"Genmao","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyang","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0384-8598","authenticated-orcid":false,"given":"Ke","family":"Lan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, College of Life Sciences, Wuhan University, Wuhan 430072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1093\/infdis\/jiad181","article-title":"The Burden of COVID-19 in the Immunocompromised Patient: Implications for Vaccination and Needs for the Future","volume":"228","author":"Antinori","year":"2023","journal-title":"J. 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