{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T12:28:09Z","timestamp":1786364889894,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,7]]},"group-title":"Immunology","reference-count":102,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["R01AI170928"],"award-info":[{"award-number":["R01AI170928"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The continued emergence of betacoronaviruses underscores the urgent need for vaccines that provide broadly protective immunity. Here, we present an epitope-focused vaccine strategy targeting the conserved S2 stem-helix region of the spike fusion machinery, a broadly neutralizing antibody-(bnAb) epitope shared across betacoronaviruses yet partially occluded on the native spike. Immunization of non-human primates with engineered S2 stem-helix nanoparticle immunogens, alone or followed by a SARS-CoV-2 BA.1 spike mRNA boost, elicited broadly cross-reactive antibody responses against sarbecoviruses, merbecoviruses, and embecoviruses and neutralized SARS-CoV-2, multiple variants, other sarbecoviruses, and MERS-CoV. Vaccine-elicited monoclonal antibodies displayed broad\n                  <jats:italic>in-vitro<\/jats:italic>\n                  neutralizing activity and protected against both SARS-CoV-2 and MERS-CoV\n                  <jats:italic>in-vivo<\/jats:italic>\n                  . Structural analyses revealed conserved features between rhesus and human stem-helix bnAbs, supporting the translational potential. Overall, our findings provide proof-of-concept that epitope-focused nanoparticle immunogens can target partially occluded, immunoquiescent bnAb epitopes, laying the groundwork for pan-betacoronavirus vaccines that provide broad protection and strengthen pandemic preparedness.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>ONE SENTENCE SUMMARY<\/jats:title>\n                  <jats:p>Epitope-focused S2 stem-helix nanoparticle immunogens elicit protective broadly neutralizing antibodies (bnAbs) against diverse betacoronaviruses in non-human primates, establishing a framework for development of pan-betacoronavirus vaccines.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.08.06.743418","type":"posted-content","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T04:05:22Z","timestamp":1786161922000},"source":"Crossref","is-referenced-by-count":0,"title":["Protective pan-betacoronavirus neutralizing antibodies by vaccination"],"prefix":"10.64898","author":[{"given":"Panpan","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA"},{"name":"Consortium for HIV\/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqi","family":"Feng","sequence":"additional","affiliation":[{"name":"Consortium for HIV\/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA"},{"name":"Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-ting","family":"He","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA"},{"name":"Consortium for HIV\/AIDS Vaccine 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