{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T16:41:12Z","timestamp":1786552872763,"version":"build-2736575974"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Pseudorabies virus (PRV) and Porcine epidemic diarrhea virus (PEDV) are currently co-circulation among swine herd with multiple variant strains, which cause severe economic losses to the global swine industry. In the present study, a recombinant PRV-based vaccine candidate was constructed backbone of a PRV variant via deletion of five genes (gI, gE, US2, US9, and TK) and insertion of the S1 gene derived from a PEDV G2b strain, and the resulting recombinant virus was generated as rPRV-\u03945-S1. The safety of the quintuple-gene-deleted PRV vector (rPRV-\u03945) was firstly evaluated in rabbits and compared with the previously generated triple-gene-deleted vector (rPRV-\u03943). Rabbits inoculated with rPRV-\u03945 exhibited milder clinical manifestations, lower viral loads in tissues, and fewer histopathological lesions, indicating an improved safety profile. Subsequent immunization trials in mice demonstrated that rPRV-\u03945-S1 induced PEDV S1-specific antibodies and PEDV-neutralizing antibodies, which were higher than those observed in the commercial inactivated PEDV vaccine group. Furthermore, rPRV-\u03945-S1 elicited higher neutralizing antibody titers against PRV variants than the Bartha-K61 vaccine and provided complete protection against lethal challenge with the PRV variant. To further validate the immunogenicity and protective efficacy of rPRV-\u03945-S1, challenge experiments were conducted in piglets. The results showed that piglets immunized with rPRV-\u03945-S1 developed detectable antibody responses against both PRV and PEDV. After challenge with the PEDV G2b variant, rPRV-\u03945-S1-immunized piglets exhibited reduced diarrhea severity, decreased viral shedding, alleviated intestinal lesions, and improved weight gain compared with control animals. Collectively, these findings demonstrate that the quintuple-gene-deleted PRV vector exhibits an improved safety profile and can serve as an effective platform for heterologous antigen delivery. The recombinant virus rPRV-\u03945-S1 can induced immune responses against both PRV and PEDV in multiple animal models, which supports its potential as a bivalent vaccine candidate against these two economically critical swine pathogens.<\/jats:p>","DOI":"10.3389\/fmicb.2026.1878909","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:59:15Z","timestamp":1783490355000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of a quintuple-gene-deleted PRV vector expressing PEDV S1: safety and immunogenicity in rabbits, mice, and piglets"],"prefix":"10.3389","volume":"17","author":[{"given":"Junda","family":"Li","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University","place":["Yangling, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiadeng","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University","place":["Yangling, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruhai","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University","place":["Yangling, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofan","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University","place":["Yangling, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Litian","family":"Shi","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University","place":["Yangling, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saba","family":"Nasir","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University","place":["Yangling, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yining","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University","place":["Yangling, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Shi","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University","place":["Yangling, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqing","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Animal Engineering\/Shaanxi Engineering Research Center of Animal Disease Prevention and Control\/The Youth Innovation Team of Shaanxi Universities, Shaanxi A&F Technology University","place":["Yangling, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinglong","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University","place":["Yangling, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"965997","DOI":"10.3389\/fmicb.2022.965997","article-title":"Efficacy of a gB + gD-based subunit vaccine and the adjuvant granulocyte-macrophage colony stimulating factor for pseudorabies virus in rabbits","volume":"13","author":"Cao","year":"2022","journal-title":"Front. 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