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We determined a crystal structure of CC40.8 Fab with a SARS-CoV-2 S2 stem peptide at 1.6-\u00c5 resolution and found that the peptide adopted a mainly helical structure. Conserved residues in \u03b2-CoVs interacted with CC40.8 antibody, thereby providing a molecular basis for its broad reactivity. CC40.8 exhibited in vivo protective efficacy against SARS-CoV-2 challenge in two animal models. In both models, CC40.8-treated animals exhibited less weight loss and reduced lung viral titers compared to controls. Furthermore, we noted that CC40.8-like bnAbs are relatively rare in human COVID-19 infection, and therefore, their elicitation may require rational structure-based vaccine design strategies. Overall, our study describes a target on \u03b2-CoV spike proteins for protective antibodies that may facilitate the development of pan\u2013\u03b2-CoV vaccines.<\/jats:p>","DOI":"10.1126\/scitranslmed.abi9215","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T09:59:13Z","timestamp":1644314353000},"source":"Crossref","is-referenced-by-count":197,"title":["A human antibody reveals a conserved site on beta-coronavirus spike proteins and confers protection against SARS-CoV-2 infection"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5740-4303","authenticated-orcid":true,"given":"Panpan","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA."},{"name":"IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA."},{"name":"Consortium for HIV\/AIDS Vaccine Development (CHAVD), The 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