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The conserved S2 subunit presents a promising vaccine target for broad and durable protection, but the immunodominance in vaccine\u2010induced germinal center (GC) responses hinders effective antibody generation against S2. Here, a polymeric toll\u2010like receptor 7 agonist nanoparticle (TLR7\u2010NP) adjuvant is reported, well designed to enhance lymph node targeting and more efficiently activate S2\u2010specific B cells. When combined with Alum\u2010adsorbed SARS\u2010CoV\u20102 HexaPro spike protein, TLR7\u2010NP promotes early GC recruitment of S2\u2010specific B cells and overcomes\u00a0the immunodominance, leading to early and robust S2\u2010specific antibody responses. Compared to conventional TLR7\u2010Alum adjuvanted subunit vaccine and clinically used SARS\u2010CoV\u20102 mRNA vaccine, TLR7\u2010NP adjuvant induces stronger humoral immune responses across sarbecoviruses and betacoronaviruses and promotes long\u2010lived plasma cell and memory B cell formation. These findings present a direct B cell\u2010activating adjuvant approach for effective pan\u2010coronavirus vaccine development.<\/jats:p>","DOI":"10.1002\/advs.202512100","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T17:43:58Z","timestamp":1764092638000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nanoparticle Adjuvant Design Enhances Germinal Center Responses Targeting Conserved Subdominant Epitopes for Pan\u2010Coronavirus Vaccine Development"],"prefix":"10.1002","volume":"13","author":[{"given":"Sijin","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering The University of Texas at Austin  Austin TX 78712 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanella M.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The University of Texas at Austin  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