{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T20:59:20Z","timestamp":1776113960610,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Henan Provincial Higher Education Institutions Key Scientific Research Project","award":["26B230017"],"award-info":[{"award-number":["26B230017"]}]},{"name":"Scientific and Technological Project Plan of the Corps","award":["2024AB034"],"award-info":[{"award-number":["2024AB034"]}]},{"name":"Scientific and Technological Project Plan of the Corps","award":["2025AB083"],"award-info":[{"award-number":["2025AB083"]}]},{"name":"Central Guidance for Local Technology Development Fund","award":["2025YD013"],"award-info":[{"award-number":["2025YD013"]}]},{"name":"Science and Technology Plan Project of Xinjiang Uygur Autonomous Region","award":["2024LQ02007"],"award-info":[{"award-number":["2024LQ02007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Bovine viral diarrhea virus (BVDV) is a major pathogen inflicting substantial economic losses on the global cattle industry. To develop a more effective vaccine, we constructed two novel bicistronic recombinant adenoviruses, rAdV-I E0+I E2 and rAdV-I E2+II E2, and systematically evaluated their immunogenicity and protective efficacy in BALB\/c mice. Both vaccine candidates, particularly rAdV-I E2+II E2, provoked a robust and rapid neutralizing antibody response that was significantly superior to a commercial inactivated vaccine. They also elicited a potent Th1-skewed cellular immune response, as indicated by significantly higher IFN-\u03b3 secretion, and a balanced profile of BVDV-specific IgG and its subclasses. Upon BVDV challenge, immunization with both recombinant vaccines, especially rAdV-I E2+II E2, resulted in a comprehensive reduction in viral loads across all tested tissues (blood, spleen, lungs, kidneys, and small intestine), demonstrating broader protection than the inactivated vaccine. Concordantly, histopathological analysis confirmed that vaccination preserved the normal architecture of the duodenum and spleen, preventing the significant pathological damage observed in the rAdV-empty negative control group. Our findings demonstrate that these adenovirus-vectored vaccines, particularly rAdV-I E2+II E2, induce a multifaceted and protective immune response, highlighting their promise as superior candidates against BVDV.<\/jats:p>","DOI":"10.3390\/microorganisms14020378","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T10:35:37Z","timestamp":1770287737000},"page":"378","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel Bicistronic Adenovirus Vaccine Elicits Superior and Comprehensive Protection Against BVDV"],"prefix":"10.3390","volume":"14","author":[{"given":"Mingguo","family":"Xu","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuangfu","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hengyun","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueyu","family":"Tao","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongchen","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0020-7231","authenticated-orcid":false,"given":"Ningning","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832000, China"},{"name":"College of Animal Science and Technology, Xinyang Agriculture and Forestry University, Xinyang 464000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1099\/jgv.0.000672","article-title":"ICTV Virus Taxonomy Profile: Flaviviridae","volume":"98","author":"Simmonds","year":"2017","journal-title":"J. Gen. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2426","DOI":"10.1111\/tbed.13300","article-title":"Epidemiological factors and mitigation measures influencing production losses in cattle due to bovine viral diarrhoea virus infection: A meta-analysis","volume":"66","author":"Pinior","year":"2019","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1017\/S146625231500002X","article-title":"HoBi-like viruses\u2014The typical \u2018atypical bovine pestivirus\u2019","volume":"16","author":"Bauermann","year":"2015","journal-title":"Anim. Health Res. Rev."},{"key":"ref_4","first-page":"69","article-title":"Genetic characterization and clinical characteristics of bovine viral diarrhea viruses in cattle herds of Heilongjiang province, China","volume":"23","author":"Zhou","year":"2022","journal-title":"Iran. J. Vet. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.vetimm.2014.04.007","article-title":"Immunogenicity of an inactivated Chinese bovine viral diarrhea virus 1a (BVDV 1a) vaccine cross protects from BVDV 1b infection in young calves","volume":"160","author":"Wang","year":"2014","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_6","first-page":"539","article-title":"Attenuation of virus diarrhea virus (strain Oregon C24V) for vaccine purposes","volume":"51","author":"Coggins","year":"1961","journal-title":"Cornell Vet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4654","DOI":"10.1128\/JVI.02696-06","article-title":"Comparative seroprevalence and immunogenicity of six rare serotype recombinant adenovirus vaccine vectors from subgroups B and D","volume":"81","author":"Abbink","year":"2007","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1038\/mt.2009.130","article-title":"New insights on adenovirus as vaccine vectors","volume":"17","author":"Lasaro","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e198069","DOI":"10.1172\/jci.insight.198069","article-title":"Comparative analysis of adenovirus, mRNA, and protein vaccines reveals context-dependent immunogenicity and efficacy","volume":"10","author":"Awakoaiye","year":"2025","journal-title":"JCI Insight"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"126959","DOI":"10.1016\/j.vaccine.2025.126959","article-title":"A novel tetravalent influenza vaccine based on one chimpanzee adenoviral vector","volume":"53","author":"Niu","year":"2025","journal-title":"Vaccine"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Pekarek, M.J., Madapong, A., Wiggins, J., and Weaver, E.A. (2025). Adenoviral-Vectored Multivalent Vaccine Provides Durable Protection Against Influenza B Viruses from Victoria-like and Yamagata-like Lineages. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26041538"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Muravyeva, A., and Smirnikhina, S. (2024). Adenoviral vectors for gene therapy of hereditary diseases. Biology, 13.","DOI":"10.3390\/biology13121052"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"110633","DOI":"10.1016\/j.vetmic.2025.110633","article-title":"A recombinant adenovirus-vectored PEDV vaccine co-expressing S1 and N proteins enhances mucosal immunity and confers protection in piglets","volume":"308","author":"Luo","year":"2025","journal-title":"Vet. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6221","DOI":"10.1016\/j.vaccine.2019.08.017","article-title":"Duration of protection and humoral immunity induced by an adenovirus-vectored subunit vaccine for foot-and-mouth disease (FMD) in Holstein steers","volume":"37","author":"Sitt","year":"2019","journal-title":"Vaccine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1016\/S0264-410X(02)00745-4","article-title":"DNA vaccination against bovine viral diarrhoea virus induces humoral and cellular responses in cattle with evidence for protection against viral challenge","volume":"21","author":"Nobiron","year":"2003","journal-title":"Vaccine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5591","DOI":"10.1016\/j.vaccine.2018.07.054","article-title":"Enhanced immune responses to E2 protein and DNA formulated with ISA 61 VG administered as a DNA prime-protein boost regimen against bovine viral diarrhea virus","volume":"36","author":"Cai","year":"2018","journal-title":"Vaccine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jbiotec.2018.01.016","article-title":"The construction of recombinant Lactobacillus casei expressing BVDV E2 protein and its immune response in mice","volume":"270","author":"Bhuyan","year":"2018","journal-title":"J. Biotechnol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Aberle, D., Muhle-Goll, C., B\u00fcrck, J., Wolf, M., Rei\u00dfer, S., Luy, B., Wenzel, W., Ulrich, A.S., and Meyers, G. (2014). Structure of the membrane anchor of pestivirus glycoprotein E(rns), a long tilted amphipathic helix. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1003973"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/0378-1135(93)90028-6","article-title":"Immunogens of bovine viral diarrhea virus","volume":"37","author":"Bolin","year":"1993","journal-title":"Vet. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s12985-020-01338-6","article-title":"Experimental immunization of mice with a recombinant bovine enterovirus vaccine expressing BVDV E0 protein elicits a long-lasting serologic response","volume":"17","author":"Ren","year":"2020","journal-title":"Virol. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/j.1574-6968.1999.tb13727.x","article-title":"Recombinant adenoviruses expressing the E2 protein of bovine viral diarrhea virus induce humoral and cellular immune responses","volume":"177","author":"Elahi","year":"1999","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/viro.1999.9828","article-title":"Induction of humoral and cellular immune responses against the nucleocapsid of bovine viral diarrhea virus by an adenovirus vector with an inducible promoter","volume":"261","author":"Elahi","year":"1999","journal-title":"Virology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","article-title":"A simple method of estimating fifty percent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Epidemiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1007\/s007050050569","article-title":"Investigation of the immunological properties of the bovine viral diarrhea virus protein NS3 expressed by an adenovirus vector in mice","volume":"144","author":"Elahi","year":"1999","journal-title":"Arch. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2175558","DOI":"10.1080\/21645515.2023.2175558","article-title":"Preclinical immunogenicity of an adenovirus-vectored vaccine for herpes zoster","volume":"19","author":"Ulaszewska","year":"2023","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Xu, M.G., Wu, A.D., Liu, J.N., Yang, Z.L., Li, H.H., Ma, H.L., Yang, N.N., Sheng, J.L., and Chen, C.F. (2025). Inactivated vaccines derived from bovine viral diarrhea virus B3 strain elicit robust and specific humoral and cellular immune responses. Front. Microbiol., 16.","DOI":"10.3389\/fmicb.2025.1607334"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.virol.2023.05.001","article-title":"Recombinant human adenovirus type 5 based vaccine candidates against GIIa-and GIIb-genotype porcine epidemic diarrhea virus induce robust humoral and cellular response in mice","volume":"584","author":"Miao","year":"2023","journal-title":"Virology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1590\/S0100-879X2007000600010","article-title":"Recombinant E2 glycoprotein of bovine viral diarrhea virus induces a solid humoral neutralizing immune response but fails to confer total protection in cattle","volume":"40","author":"Leunda","year":"2007","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s12985-022-01851-w","article-title":"The recombinant Erns and truncated E2-based indirect enzyme-linked immunosorbent assays to distinguishably test specific antibodies against classical swine fever virus and bovine viral diarrhea virus","volume":"19","author":"Yi","year":"2022","journal-title":"Virol. J."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Zhang, K., Zhang, J., Qiu, Z., Zhang, K., Liang, F., Zhou, Q., Wang, L., and Li, J. (2022). Prevalence characteristic of BVDV in some large scale dairy farms in Western China. Front. Vet. Sci., 9.","DOI":"10.3389\/fvets.2022.961337"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1007\/s00705-025-06304-7","article-title":"Molecular detection and genotyping of bovine viral diarrhea virus in four provinces of China","volume":"170","author":"Liu","year":"2025","journal-title":"Arch. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.vetmic.2012.04.023","article-title":"High prevalence of bovine viral diarrhea virus 1 in Chinese swine herds","volume":"159","author":"Deng","year":"2012","journal-title":"Vet. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Yang, N., Zhang, J., Xu, M., Yi, J., Wang, Z., Wang, Y., and Chen, C. (2022). Virus-like particles vaccines based on glycoprotein E0 and E2 of bovine viral diarrhea virus induce humoral responses. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.1047001"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wang, Z., Liu, M., Zhao, H., Wang, P., Ma, W., Zhang, Y., Wu, W., and Peng, C. (2021). Induction of robust and specific humoral and cellular immune responses by bovine viral diarrhea virus virus-like particles (BVDV-VLPs) engineered with baculovirus expression vector system. Vaccines, 9.","DOI":"10.3390\/vaccines9040350"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/2\/378\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T10:52:01Z","timestamp":1770288721000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/2\/378"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,5]]},"references-count":34,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["microorganisms14020378"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms14020378","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,5]]}}}