{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T22:43:37Z","timestamp":1773009817296,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":160,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transboundary and Emerging Diseases"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>Mucosal vaccines are powerful tools for combatting emerging infectious diseases, particularly mucosal\u2010associated pathogens. However, one of the main bottlenecks in developing mucosal vaccines is the lack of accurate animal models. In this study, a vesicular stomatitis virus (VSV)\u2010vectored Middle East respiratory syndrome coronavirus (MERS\u2010CoV) mucosal vaccine was designed for investigations. Compared with the VSV backbone, rVSV\u0394G\u2010MERS\u2010S exhibited altered cellular tropism, as determined by MERS\u2010S. In wild\u2010type (WT) C57BL\u20106J mice and hamsters, the nasal spray of rVSV\u0394G\u2010MERS\u2010S was poorly immunogenic. In contrast, rVSV\u0394G\u2010MERS\u2010S was highly immunogenic in transgenic mice (hDPP4 mice) and hDPP4\u2010transduced hamsters harboring the functional MERS\u2010CoV receptor. Compared with those of WT C57BL\u20106J mice, the nasal spray of rVSV\u0394G\u2010MERS\u2010S resulted in effective antigen\u2010presenting cell (APC) priming, Tfh\u2010GcB\u2010plasma cell (pC) proliferation, and robust humoral and cellular responses, together with the activation of antiviral signaling pathways in hDPP4 mice. Similarly, rVSV\u0394G\u2010MERS\u2010S was highly immunogenic in alpacas and rhesus monkeys, which are naturally susceptible to MERS\u2010CoV and harbor the effective DPP4 receptor. The alignment of hDPP4 receptors in these animals revealed that L294, I295, and R336 in DPP4 are key residues contributing to differences in sensitivity across species. Consistently, a high binding affinity was observed between human, alpacas, and rhesus monkey DPP4 receptors and MERS\u2010CoV receptor binding domains (RBDs) compared with that of mice and hamster. Overall, this proof\u2010of\u2010concept study not only guides the selection of appropriate animal models for the evaluation of mucosal vaccines of MERS but also provides evidence that functional receptors DPP4 in animal models are prerequisites for the immune performance of the MERS mucosal vaccine.<\/jats:p>","DOI":"10.1155\/tbed\/2303502","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T08:05:39Z","timestamp":1749542739000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Functional DPP4 Receptor Is an Indispensable Factor Mediating the Immune Performance of Mucosal Vaccines for Middle East Respiratory 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