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Efforts to prepare for future\n                    <jats:italic>Merbecovirus<\/jats:italic>\n                    spillover events require vaccines that protect beyond a single virus strain. To evaluate antigenic conservation and cross\u2010protective potential, SpyCatcher\u2010mi3 nanoparticles displaying the receptor\u2010binding domain and subdomain 1 (RBD\u2010SD1) from three DPP4\u2010using merbecoviruses, MERS\u2010CoV, NL140422, and HKU4, were generated. Female mice immunized with these nanoparticle vaccines elicited robust IgG antibody endpoint binding titers and cross\u2010reactive antibody responses against the three merbecoviruses. Only the MERS\u2010CoV RBD\u2010SD1 vaccine, however, elicited neutralizing antibodies against MERS\u2010CoV. While vaccination with MERS\u2010CoV RBD\u2010SD1 reduced lung viral titers in MERS\u2010CoV\u2010challenged human DPP4 mice below the limit of detection, no significant reduction in virus titers was seen in NL140422\u2010 and HKU4\u2010RBD\u2010SD1\u2010vaccine\u2010immunized mice. These findings indicate that while the RBD\u2010SD1 interface presents conserved antigenic features sufficient for serological cross\u2010recognition, these epitopes may not be functionally immunodominant for cross\u2010neutralization.\n                  <\/jats:p>","DOI":"10.1002\/bit.70180","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:42:08Z","timestamp":1773013328000},"page":"1338-1349","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RBD\u2010SD1 Nanoparticle Vaccines From DPP4\u2010Using Merbecoviruses Elicit a Cross\u2010Reactive Antibody Response but Limited Cross\u2010Protective Immunity"],"prefix":"10.1002","volume":"123","author":[{"given":"Peter J.","family":"Halfmann","sequence":"first","affiliation":[{"name":"Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute University of Wisconsin Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Soo","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Chemical &amp; Biomolecular Engineering Georgia Institute of Technology Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute University of Wisconsin Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augustine","family":"Duffy","sequence":"additional","affiliation":[{"name":"School of Chemical &amp; Biomolecular Engineering Georgia Institute of Technology Atlanta Georgia USA"},{"name":"Parker H. 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