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Although multimeric display of the receptor\u2010binding domain (RBD) using exogenous scaffolds improve immune responses, such approaches may elicit off\u2010target immune responses against the scaffolds themselves and remain limited by rapid RBD antigenic drift. Here, we report the rational design of a self\u2010assembling trimeric subunit vaccine, termed RBD\u2010heptad repeat 1 (HR1)\u2010stem helix (SH)\u2010heptad repeat 2 (HR2) (RHS), which integrates the JN.1 RBD with a highly conserved SH epitope from SARS\u2010CoV\u20102 within a native HR1\u2010HR2 trimeric scaffold via optimized linkers. RHS exhibits high structural stability, efficient trimerization, and enhanced antigen presentation. In mice, RHS elicits robust humoral and cellular immune responses, including potent cross\u2010 neutralizing antibodies against diverse SARS\u2010CoV\u20102 variants and pan\u2010betacoronavirus SH\u2010specific antibodies. In K18\u2010hACE2 mice, RHS confers strong protection against both antigen\u2010matched and antigen\u2010mismatched Omicron variants, while intranasal immunization induces potent mucosal IgA and IgG responses. Furthermore, the modular RHS platform is readily adaptable to antigens from SARS\u2010CoV and MERS\u2010CoV, underscoring its versatility for pan\u2010coronavirus vaccine development. Together, these findings establish RHS as a generalizable strategy for overcoming viral immune evasion and advancing next\u2010generation vaccine design.<\/jats:p>","DOI":"10.1002\/advs.77384","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T04:50:57Z","timestamp":1788324657000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Engineered HR1\u2010Stem Helix\u2010HR2 Trimeric Platform for Developing Broad\u2010Spectrum Coronavirus Vaccines"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4581-7887","authenticated-orcid":false,"given":"Xikui","family":"Sun","sequence":"first","affiliation":[{"name":"State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory Disease Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University  Guangzhou China"},{"name":"Guangzhou National 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