{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:10:16Z","timestamp":1787242216864,"version":"build-2736575974"},"posted":{"date-parts":[[2025,10,1]]},"group-title":"Bioengineering","reference-count":108,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["P01AI65072"],"award-info":[{"award-number":["P01AI65072"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["U19AI135995"],"award-info":[{"award-number":["U19AI135995"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014989","name":"Chan Zuckerberg Initiative","doi-asserted-by":"crossref","award":["2022-310965"],"award-info":[{"award-number":["2022-310965"]}],"id":[{"id":"10.13039\/100014989","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009070","name":"Hans Sigrist Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009070","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Corning, Inc."},{"DOI":"10.13039\/100008548","name":"Harvard T.H. Chan School of Public Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008548","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Four seasonal endemic human coronaviruses (EhCoVs), HKU1-CoV, OC43-CoV, 229E-CoV, and NL63-CoV, are culprits of mild upper respiratory and periodic severe diseases in vulnerable populations. Despite their prevalence, understanding EhCoVs\u2019 antigenic and immune signatures remains elusive. SARS-CoV-2 has evolved as the fifth EhCoV, requiring seasonal vaccination in most parts of the world, and currently, no other EhCoV vaccines are available. SARS-CoV-2 co-infection with EhCoVs increases disease severity; thus, combined vaccination may provide increased protection against seasonal EhCoVs overall. Here, we explored Spike (S) receptor binding domain (RBD) vs. N-terminal domain (NTD) B-cell immunodominance in EhCoV-positive convalescent donors and immunogenicity in mice. We found that while antibody and B-cell isotypes were relatively dominant to S NTD, mice immunized with S RBD elicited significantly higher binding and neutralizing antibody (nAb) responses. With that knowledge, we used computational methods to infer that EhCoV S sequences evolve into two main clades and designed chimeric immunodominant domains (IDDs) from both clades for each EhCoV. IDDs were scaffolded onto two-component nanoparticles (NPs) displaying each IDD separately (monovalent IDD NP); three \u00df-EhCoV IDDs (Mosaic-3 IDD NP); or five EhCoVs IDDs (Mosaic-5 IDD NP). Mice immunized with mosaic IDD NPs, but not soluble IDD antigens nor monovalent IDD NPs, elicited potent, broadly cross-reactive binding and neutralizing antibody (Ab) responses against SARS-CoV-2 variants, other EhCoVs, and Sarbecoviruses. System serology revealed that all four IDD immunogens elicited distinct Ab subclasses and Fc-effector functions, with mosaic-5 IDD NPs eliciting the most\n                  <jats:italic>de novo<\/jats:italic>\n                  Ab subclasses, distributions, and broader Fc-mediated immune mechanisms. Dissection of vaccine-immune sera revealed polyclonal Ab responses against multiple non-overlapping cross-reactive S epitopes. Due to elicitation of broad Ab responses with combinatory functionality, IDD NPs open new horizons for developing first-in-class supraseasonal EhCoV vaccine candidates, with potential to decrease frequent SARS-CoV-2 sequence updates and protect against other EhCoVs. Moreover, elicitation of Ab breadth that spans pandemic-threat Sarbecoviruses gives mosaic IDD NPs promise towards pandemic preparedness.\n                <\/jats:p>","DOI":"10.1101\/2025.10.01.679649","type":"posted-content","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T03:35:24Z","timestamp":1759376124000},"source":"Crossref","is-referenced-by-count":1,"title":["Rational Design of Multiclade Coronavirus Spike Immunodominant Domain Nanoparticles to Elicit Broad Antibody Responses"],"prefix":"10.64898","author":[{"given":"Christian K.O.","family":"Dzuvor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney","family":"Moak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay 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