{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:27:56Z","timestamp":1791257276571,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T00:00:00Z","timestamp":1698192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"United States Department of Agriculture\/National Institute of Food and Agriculture","award":["2019-67015-29867"],"award-info":[{"award-number":["2019-67015-29867"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Classical swine fever (CSF) remains one of the most economically significant viral diseases affecting domestic pigs and wild boars worldwide. To develop a safe and effective vaccine against CSF, we have constructed a triple gene-deleted pseudorabies virus (PRVtmv)-vectored bivalent subunit vaccine against porcine circovirus type 2b (PCV2b) and CSFV (PRVtmv+). In this study, we determined the protective efficacy of the PRVtmv+ against virulent CSFV challenge in pigs. The results revealed that the sham-vaccinated control group pigs developed severe CSFV-specific clinical signs characterized by pyrexia and diarrhea, and became moribund on or before the seventh day post challenge (dpc). However, the PRVtmv+-vaccinated pigs survived until the day of euthanasia at 21 dpc. A few vaccinated pigs showed transient diarrhea but recovered within a day or two. One pig had a low-grade fever for a day but recovered. The sham-vaccinated control group pigs had a high level of viremia, severe lymphocytopenia, and thrombocytopenia. In contrast, the vaccinated pigs had a low\u2013moderate degree of lymphocytopenia and thrombocytopenia on four dpc, but recovered by seven dpc. Based on the gross pathology, none of the vaccinated pigs had any CSFV-specific lesions. Therefore, our results demonstrated that the PRVtmv+ vaccinated pigs are protected against virulent CSFV challenge.<\/jats:p>","DOI":"10.3390\/v15112143","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T04:14:47Z","timestamp":1698207287000},"page":"2143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Triple Gene-Deleted Pseudorabies Virus-Vectored Subunit PCV2b and CSFV Vaccine Protect Pigs against a Virulent CSFV Challenge"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5155-1361","authenticated-orcid":false,"given":"Ediane","family":"Silva","sequence":"first","affiliation":[{"name":"US Department of Agricultural, ARS, Plum Island Animal Disease Center, Orient, NY 11957, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Medina-Ramirez","sequence":"additional","affiliation":[{"name":"US Department of Agricultural, ARS, Plum Island Animal Disease Center, Orient, NY 11957, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6804-0808","authenticated-orcid":false,"given":"Selvaraj","family":"Pavulraj","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7894-0233","authenticated-orcid":false,"given":"Douglas P.","family":"Gladue","sequence":"additional","affiliation":[{"name":"US Department of Agricultural, ARS, Plum Island Animal Disease Center, Orient, NY 11957, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Borca","sequence":"additional","affiliation":[{"name":"US Department of Agricultural, ARS, Plum Island Animal Disease Center, Orient, NY 11957, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8008-5512","authenticated-orcid":false,"given":"Shafiqul I.","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Blome, S., Staubach, C., Henke, J., Carlson, J., and Beer, M. (2017). Classical Swine Fever-An Updated Review. Viruses, 9.","DOI":"10.3390\/v9040086"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1111\/tbed.12676","article-title":"Epidemiology, diagnosis and control of classical swine fever: Recent developments and future challenges","volume":"65","author":"Postel","year":"2018","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0167-5877(99)00079-3","article-title":"A model to estimate the financial consequences of classical swine fever outbreaks: Principles and outcomes","volume":"42","author":"Meuwissen","year":"1999","journal-title":"Prev. Vet. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0378-1135(00)00144-9","article-title":"The 1997-1998 epidemic of classical swine fever in the Netherlands","volume":"73","author":"Stegeman","year":"2000","journal-title":"Vet. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2907.2007.00097.x","article-title":"Potential ecological and epidemiological factors affecting the persistence of classical swine fever in wild boar Sus scrofa populations","volume":"37","author":"THULKE","year":"2007","journal-title":"Mammal. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"198151","DOI":"10.1016\/j.virusres.2020.198151","article-title":"Classical swine fever virus: The past, present and future","volume":"289","author":"Ganges","year":"2020","journal-title":"Virus Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3389\/fvets.2018.00031","article-title":"A Review of Classical Swine Fever Virus and Routes of Introduction into the United States and the Potential for Virus Establishment","volume":"5","author":"Brown","year":"2018","journal-title":"Front. Vet. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Coronado, L., Perera, C.L., Rios, L., Fr\u00edas, M.T., and P\u00e9rez, L.J. (2021). A Critical Review about Different Vaccines against Classical Swine Fever Virus and Their Repercussions in Endemic Regions. Vaccines, 9.","DOI":"10.3390\/vaccines9020154"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.vetmic.2009.11.020","article-title":"An update on safety studies on the attenuated \"RIEMSER Schweinepestoralvakzine\" for vaccination of wild boar against classical swine fever","volume":"143","author":"Kaden","year":"2010","journal-title":"Vet. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Rossi, S., Staubach, C., Blome, S., Guberti, V., Thulke, H.H., Vos, A., Koenen, F., and Le Potier, M.F. (2015). Controlling of CSFV in European wild boar using oral vaccination: A review. Front. Microbiol., 6.","DOI":"10.3389\/fmicb.2015.01141"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1016\/S0264-410X(00)00027-X","article-title":"Recombinant classical swine fever (CSF) viruses derived from the Chinese vaccine strain (C-strain) of CSF virus retain their avirulent and immunogenic characteristics","volume":"18","author":"Miedema","year":"2000","journal-title":"Vaccine"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1128\/jvi.71.2.1735-1735.1997","article-title":"Recovery of cytopathogenic and noncytopathogenic bovine viral diarrhea viruses from cDNA constructs","volume":"71","author":"Meyers","year":"1997","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.virol.2004.01.028","article-title":"An avirulent chimeric Pestivirus with altered cell tropism protects pigs against lethal infection with classical swine fever virus","volume":"322","author":"Reimann","year":"2004","journal-title":"Virology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.vaccine.2011.10.064","article-title":"Innocuousness and safety of classical swine fever marker vaccine candidate CP7_E2alf in non-target and target species","volume":"30","author":"Konig","year":"2011","journal-title":"Vaccine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1111\/j.1751-0813.2000.tb11862.x","article-title":"Aujeszky\u2019s disease eradication in New Zealand","volume":"78","author":"MacDiarmid","year":"2000","journal-title":"Aust. Vet. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1046\/j.1439-0450.2003.00666.x","article-title":"Eradication of Aujeszky\u2019s disease in Germany","volume":"50","author":"Muller","year":"2003","journal-title":"J. Vet. Med. B Infect. Dis. Vet. Public. Health"},{"key":"ref_17","unstructured":"OIE (2023, October 12). OIE World Animal Health Information System. Available online: https:\/\/wahis.woah.org\/#\/dashboards\/country-or-disease-dashboard."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1007\/s12250-020-00340-0","article-title":"Current Status and Challenge of Pseudorabies Virus Infection in China","volume":"36","author":"Tan","year":"2021","journal-title":"Virol. Sin."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Liu, A., Xue, T., Zhao, X., Zou, J., Pu, H., Hu, X., and Tian, Z. (2022). Pseudorabies Virus Associations in Wild Animals: Review of Potential Reservoirs for Cross-Host Transmission. Viruses, 14.","DOI":"10.3390\/v14102254"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Pacini, M.I., Forzan, M., Cilia, G., Bernardini, L., Marzoli, F., Pedonese, F., Bandecchi, P., Fratini, F., and Mazzei, M. (2020). Detection of Pseudorabies Virus in Wild Boar Foetus. Animals, 10.","DOI":"10.3390\/ani10020366"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Pedersen, K., Turnage, C.T., Gaston, W.D., Arruda, P., Alls, S.A., and Gidlewski, T. (2018). Pseudorabies detected in hunting dogs in Alabama and Arkansas after close contact with feral swine (Sus scrofa). BMC Vet. Res., 14.","DOI":"10.1186\/s12917-018-1718-3"},{"key":"ref_22","unstructured":"Zimmerman, J.J. (2012). Diseases of Swine, Wiley-Blackwell. [10th ed.]."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1089\/vim.2020.0025","article-title":"Prevalence of Porcine Pseudorabies Virus and Its Coinfection Rate in Heilongjiang Province in China from 2013 to 2018","volume":"33","author":"Zhou","year":"2020","journal-title":"Viral Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"363","DOI":"10.4142\/jvs.2013.14.3.363","article-title":"Emergence of virulent pseudorabies virus infection in northern China","volume":"14","author":"Wu","year":"2013","journal-title":"J. Vet. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1111\/tbed.13813","article-title":"Emergence of a novel pathogenic recombinant virus from Bartha vaccine and variant pseudorabies virus in China","volume":"68","author":"Bo","year":"2021","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Delva, J.L., Nauwynck, H.J., Mettenleiter, T.C., and Favoreel, H.W. (2020). The Attenuated Pseudorabies Virus Vaccine Strain Bartha K61: A Brief Review on the Knowledge Gathered During 60 Years of Research. Pathogens, 9.","DOI":"10.3390\/pathogens9110897"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Pavulraj, S., Pannhorst, K., Stout, R.W., Paulsen, D.B., Carossino, M., Meyer, D., Becher, P., and Chowdhury, S.I. (2022). A Triple Gene-Deleted Pseudorabies Virus-Vectored Subunit PCV2b and CSFV Vaccine Protects Pigs against PCV2b Challenge and Induces Serum Neutralizing Antibody Response against CSFV. Vaccines, 10.","DOI":"10.3390\/vaccines10020305"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.virol.2005.08.015","article-title":"Mutation of E1 glycoprotein of classical swine fever virus affects viral virulence in swine","volume":"343","author":"Risatti","year":"2005","journal-title":"Virology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3787","DOI":"10.1128\/JVI.79.6.3787-3796.2005","article-title":"The E2 glycoprotein of classical swine fever virus is a virulence determinant in swine","volume":"79","author":"Risatti","year":"2005","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.virol.2008.10.039","article-title":"Development of a live attenuated antigenic marker classical swine fever vaccine","volume":"384","author":"Holinka","year":"2009","journal-title":"Virology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","article-title":"A simple method of estimating fifty per cent endpoints12","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Epidemiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0378-1135(91)90118-Y","article-title":"The development of an international reference panel of monoclonal antibodies for the differentiation of hog cholera virus from other pestiviruses","volume":"29","author":"Edwards","year":"1991","journal-title":"Vet. Microbiol."},{"key":"ref_33","unstructured":"OIE (2023, March 24). Classical Swine Fever (Infection with Classical Swine Fever Virus). Available online: https:\/\/www.woah.org\/fileadmin\/Home\/fr\/Health_standards\/tahm\/3.09.03_CSF.pdf."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.5713\/ajas.17.0037","article-title":"Blood haematology, muscle pH and serum cortisol changes in pigs with different levels of drip loss","volume":"30","author":"Koomkrong","year":"2017","journal-title":"Asian-Australas. J. Anim. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Pavulraj, S., Stout, R.W., Paulsen, D.B., and Chowdhury, S.I. (2023). Live Triple Gene-Deleted Pseudorabies Virus-Vectored Subunit PCV2b and CSFV Vaccine Undergoes an Abortive Replication Cycle in the TG Neurons following Latency Reactivation. Viruses, 15.","DOI":"10.3390\/v15020473"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0378-1135(00)00138-3","article-title":"Classical swine fever: The global situation","volume":"73","author":"Edwards","year":"2000","journal-title":"Vet. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0378-1135(00)00254-6","article-title":"Epidemiology of classical swine fever in Germany in the 1990s","volume":"77","author":"Fritzemeier","year":"2000","journal-title":"Vet Microbiol"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1099\/vir.0.023200-0","article-title":"Molecular epidemiology of current classical swine fever virus isolates of wild boar in Germany","volume":"91","author":"Leifer","year":"2010","journal-title":"J. Gen. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"de Oliveira, L.G., Gatto, I.R.H., Mechler-Dreibi, M.L., Almeida, H.M.S., Sonalio, K., and Storino, G.Y. (2020). Achievements and Challenges of Classical Swine Fever Eradication in Brazil. Viruses, 12.","DOI":"10.3390\/v12111327"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Graham, S.P., Everett, H.E., Haines, F.J., Johns, H.L., Sosan, O.A., Salguero, F.J., Clifford, D.J., Steinbach, F., Drew, T.W., and Crooke, H.R. (2012). Challenge of Pigs with Classical Swine Fever Viruses after C-Strain Vaccination Reveals Remarkably Rapid Protection and Insights into Early Immunity. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0029310"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8470","DOI":"10.1128\/jvi.68.12.8470-8476.1994","article-title":"Correlation between precolonization of trigeminal ganglia by attenuated strains of pseudorabies virus and resistance to wild-type virus latency","volume":"68","author":"Schang","year":"1994","journal-title":"J. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"808527","DOI":"10.3389\/fimmu.2021.808527","article-title":"Potentiating Lung Mucosal Immunity Through Intranasal Vaccination","volume":"12","author":"Nelson","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Zhang, F., Peng, B., Chang, H., Zhang, R., Lu, F., Wang, F., Fang, F., and Chen, Z. (2016). Intranasal Immunization of Mice to Avoid Interference of Maternal Antibody against H5N1 Infection. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157041"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/11\/2143\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:11:14Z","timestamp":1760130674000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/11\/2143"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,25]]},"references-count":43,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["v15112143"],"URL":"https:\/\/doi.org\/10.3390\/v15112143","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,25]]}}}