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However, there is no commercially available vaccine which prevents coinfection with PCV2, PCV3, and PCV4. The development of a vaccine expressing capsid (Cap) fusion proteins of multiple PCVs represents a promising approach for broadly preventing infection with PCVs. In this study, we developed a PCV subunit vaccine candidate (Cap 2-3-4) by predicting, screening, and fusing antigenic epitopes of Cap proteins of PCV2, PCV3, and PCV4. Immunoprotection assays showed that the prokaryotic expression of Cap 2-3-4 could effectively induce high levels of PCV2, PCV3, and PCV4 Cap-specific antibodies and successfully neutralize both PCV2 and PCV3. Furthermore, Cap 2-3-4 demonstrated a potent ability to activate cellular immunity and thus prevent lung damage in mice. This study provides a new option for the development of broad vaccines against PCVs.<\/jats:p>","DOI":"10.3390\/v16121964","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T04:33:29Z","timestamp":1734928409000},"page":"1964","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Subunit Vaccine Harboring the Fusion Capsid Proteins of Porcine Circovirus Types 2, 3, and 4 Induces Protective Immune Responses in a Mouse Model"],"prefix":"10.3390","volume":"16","author":[{"given":"Qikai","family":"Wang","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0631-7167","authenticated-orcid":false,"given":"Libin","family":"Liang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haili","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haidong","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longlong","family":"Si","sequence":"additional","affiliation":[{"name":"Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"},{"name":"College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingchen","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"},{"name":"Department of Medicine, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.virusres.2009.02.009","article-title":"Porcine circoviruses\u2014Small but powerful","volume":"143","author":"Finsterbusch","year":"2009","journal-title":"Virus Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ma, Z., Liu, M., Liu, Z., Meng, F., Wang, H., Cao, L., Li, Y., Jiao, Q., Han, Z., and Liu, S. (2021). Epidemiological investigation of porcine circovirus type 2 and its coinfection rate in Shandong province in China from 2015 to 2018. BMC Vet. Res., 17.","DOI":"10.1186\/s12917-020-02718-4"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ouyang, T., Zhang, X., Liu, X., and Ren, L. (2019). Co-Infection of Swine with Porcine Circovirus Type 2 and Other Swine Viruses. Viruses, 11.","DOI":"10.3390\/v11020185"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.meegid.2018.12.011","article-title":"Co-infection status of classical swine fever virus (CSFV), porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circoviruses (PCV2 and PCV3) in eight regions of China from 2016 to 2018","volume":"68","author":"Chen","year":"2019","journal-title":"Infect. Genet. Evol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.1111\/tbed.14185","article-title":"What do we know about porcine circovirus 3 (PCV3) diagnosis so far?: A review","volume":"68","author":"Tan","year":"2021","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.vetmic.2018.04.032","article-title":"Porcine circovirus type 3 (PCV3) shedding in sow colostrum","volume":"220","author":"Kedkovid","year":"2018","journal-title":"Vet. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Chen, X.M., Zhao, Y.Y., Liu, X.C., Han, Y.Y., Zhang, Y.H., Hou, C.Y., Zheng, L.L., Ma, S.J., and Chen, H.Y. (2023). Molecular detection and genetic characteristics of a novel porcine circovirus (porcine circovirus 4) and porcine reproductive and respiratory syndrome virus in Shaanxi and Henan Provinces of China. Comp. Immunol. Microbiol. Infect. Dis., 98.","DOI":"10.1016\/j.cimid.2023.102009"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Sirisereewan, C., Nguyen, T.C., Piewbang, C., Jittimanee, S., Kedkovid, R., and Thanawongnuwech, R. (2023). Molecular detection and genetic characterization of porcine circovirus 4 (PCV4) in Thailand during 2019\u20132020. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-32382-1"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s00705-023-05791-w","article-title":"Simultaneous detection and phylogenetic analysis of porcine epidemic diarrhea virus and porcine circovirus 4 in Henan province, China","volume":"168","author":"Li","year":"2023","journal-title":"Arch. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11262-014-1099-z","article-title":"Current understanding of genomic DNA of porcine circovirus type 2","volume":"49","author":"Lv","year":"2014","journal-title":"Virus Genes"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Dei Giudici, S., Mura, L., Bonelli, P., Hawko, S., Angioi, P.P., Sechi, A.M., Denti, S., Sulas, A., Burrai, G.P., and Madrau, M.P. (2023). Evidence of Porcine Circovirus Type 2 (PCV2) Genetic Shift from PCV2b to PCV2d Genotype in Sardinia, Italy. Viruses, 15.","DOI":"10.3390\/v15112157"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"481","DOI":"10.2478\/jvetres-2019-0071","article-title":"Molecular Detection and Genetic Diversity of porcine Circovirus Type 3 in Commercial Pig Farms in Xinjiang Province, China","volume":"63","author":"Mengfan","year":"2019","journal-title":"J. Vet. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"721","DOI":"10.4142\/jvs.2018.19.5.721","article-title":"Detection and genetic characterization of porcine circovirus 3 from aborted fetuses and pigs with respiratory disease in Korea","volume":"19","author":"Kim","year":"2018","journal-title":"J. Vet. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"114350","DOI":"10.1016\/j.jviromet.2021.114350","article-title":"Detection of a novel porcine circovirus 4 in Korean pig herds using a loop-mediated isothermal amplification assay","volume":"299","author":"Kim","year":"2022","journal-title":"J. Virol. Methods"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1146\/annurev-animal-031412-103720","article-title":"Porcine circovirus type 2 (PCV2): Pathogenesis and interaction with the immune system","volume":"1","author":"Meng","year":"2013","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/j.ijbiomac.2022.07.204","article-title":"Expression and immunogenicity analysis of the capsid proteins of porcine circovirus types 2 to 4","volume":"218","author":"Ji","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1099\/0022-1317-81-9-2281","article-title":"Open reading frame 2 of porcine circovirus type 2 encodes a major capsid protein","volume":"81","author":"Nawagitgul","year":"2000","journal-title":"J. Gen. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.jconrel.2024.01.017","article-title":"Protein subunit vaccines: Promising frontiers against COVID-19","volume":"366","author":"Chavda","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/s11427-022-2230-4","article-title":"Current progress in the development of prophylactic and therapeutic vaccines","volume":"66","author":"Li","year":"2023","journal-title":"Sci. China Life Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1099\/jgv.0.001087","article-title":"Purification and characterization of immunogenic recombinant virus-like particles of porcine circovirus type 2 expressed in silkworm pupae","volume":"99","author":"Masuda","year":"2018","journal-title":"J. Gen. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jbiotec.2016.02.025","article-title":"Production of Escherichia coli-based virus-like particle vaccine against porcine circovirus type 2 challenge in piglets: Structure characterization and protective efficacy validation","volume":"223","author":"Xi","year":"2016","journal-title":"J. Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4031","DOI":"10.1016\/j.vaccine.2009.04.028","article-title":"One dose of a porcine circovirus 2 (PCV2) sub-unit vaccine administered to 3-week-old conventional piglets elicits cell-mediated immunity and significantly reduces PCV2 viremia in an experimental model","volume":"27","author":"Fort","year":"2009","journal-title":"Vaccine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/ame2.12009","article-title":"Mouse models of porcine circovirus 2 infection","volume":"1","author":"Ouyang","year":"2018","journal-title":"Anim. Models Exp. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1111\/1440-1681.12434","article-title":"Effect of atovastatin treatment on porcine circovirus 2 infection in BALB\/c mice","volume":"42","author":"Yang","year":"2015","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kiupel, M., Stevenson, G.W., Galbreath, E.J., North, A., HogenEsch, H., and Mittal, S.K. (2005). Porcine circovirus type 2 (PCV2) causes apoptosis in experimentally inoculated BALB\/c mice. BMC Vet. Res., 1.","DOI":"10.1186\/1746-6148-1-7"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"271","DOI":"10.4149\/av_2016_03_271","article-title":"Modified recombinant adenoviruses increase porcine circovirus 2 capsid protein expression and induce enhanced immune responses in mice","volume":"60","author":"Li","year":"2016","journal-title":"Acta Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.micpath.2017.06.007","article-title":"The Hsp90 inhibitor 17-DMAG decreases infection of porcine circovirus type 2 in mice","volume":"109","author":"Liu","year":"2017","journal-title":"Microb. Pathog."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4722","DOI":"10.1016\/j.vaccine.2017.07.031","article-title":"Immunogenicity of adenovirus vaccines expressing the PCV2 capsid protein in pigs","volume":"35","author":"Li","year":"2017","journal-title":"Vaccine"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kroeger, M., Vargas-Bermudez, D.S., Jaime, J., Parada, J., Groeltz, J., Gauger, P., and Pi\u00f1eyro, P. (2024). First detection of PCV4 in swine in the United States: Codetection with PCV2 and PCV3 and direct detection within tissues. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-66328-y"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1007\/s00705-021-05088-w","article-title":"Retrospective surveillance of porcine circovirus 4 in pigs in Inner Mongolia, China, from 2016 to 2018","volume":"166","author":"Ha","year":"2021","journal-title":"Arch. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"145991","DOI":"10.1016\/j.gene.2021.145991","article-title":"Simultaneous detection and genetic characterization of porcine circovirus 2 and 4 in Henan province of China","volume":"808","author":"Xu","year":"2022","journal-title":"Gene"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13567-022-01053-w","article-title":"Current knowledge on epidemiology and evolution of novel porcine circovirus 4","volume":"53","author":"Wang","year":"2022","journal-title":"Vet. Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Liu, C., Liu, Y., Feng, H., Zhao, B., Chen, Y., Huang, H., Wang, P., Deng, R., and Zhang, G. (2020). PCV cap proteins fused with calreticulin expressed into polymers in Escherichia coli with high immunogenicity in mice. BMC Vet. Res., 16.","DOI":"10.1186\/s12917-020-02527-9"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mao, Q., Zhang, W., Ma, S., Qiu, Z., Li, B., Xu, C., He, H., Fan, S., Wu, K., and Chen, J. (2021). Fusion Expression and Immune Effect of PCV2 Cap Protein Tandem Multiantigen Epitopes with CD154\/GM-CSF. Vet. Sci., 8.","DOI":"10.3390\/vetsci8100211"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1007\/s00705-020-04754-9","article-title":"Efficient application of a baculovirus-silkworm larvae expression system for obtaining porcine circovirus type 2 virus-like particles for a vaccine","volume":"165","author":"He","year":"2020","journal-title":"Arch. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"119","DOI":"10.5604\/17322693.1038351","article-title":"Prokaryotic expression systems","volume":"67","author":"Wujak","year":"2013","journal-title":"Postep. Hig. I Med. Dosw."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1099\/vir.0.067108-0","article-title":"Thirty years of baculovirus-insect cell protein expression: From dark horse to mainstream technology","volume":"96","author":"Pijlman","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.ymeth.2011.06.011","article-title":"Optimizing the baculovirus expression vector system","volume":"55","author":"Hitchman","year":"2011","journal-title":"Methods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jbiotec.2016.09.002","article-title":"Engineering the transposition-based baculovirus expression vector system for higher efficiency protein production from insect cells","volume":"238","author":"Mehalko","year":"2016","journal-title":"J. Biotechnol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Rcheulishvili, N., Mao, J., Papukashvili, D., Feng, S., Liu, C., Yang, X., Lin, J., He, Y., and Wang, P.G. (2023). Development of a Multi-Epitope Universal mRNA Vaccine Candidate for Monkeypox, Smallpox, and Vaccinia Viruses: Design and In Silico Analyses. Viruses, 15.","DOI":"10.3390\/v15051120"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/s00262-013-1516-5","article-title":"Immunologic response to the survivin-derived multi-epitope vaccine EMD640744 in patients with advanced solid tumors","volume":"63","author":"Lennerz","year":"2014","journal-title":"Cancer Immunol. Immunother. CII"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Zhang, F., Zhang, Z., Li, X., Li, J., Lv, J., Ma, Z., and Pan, L. (2021). Immune Responses to Orally Administered Recombinant Lactococcus lactis Expressing Multi-Epitope Proteins Targeting M Cells of Foot-and-Mouth Disease Virus. Viruses, 13.","DOI":"10.3390\/v13102036"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e167306","DOI":"10.1172\/jci.insight.167306","article-title":"Single-epitope T cell-based vaccine protects against SARS-CoV-2 infection in a preclinical animal model","volume":"8","author":"Tada","year":"2023","journal-title":"JCI Insight"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/cmi.2017.92","article-title":"Multi-epitope vaccines: A promising strategy against tumors and viral infections","volume":"15","author":"Zhang","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jviromet.2013.01.003","article-title":"Cellular immunogenicity of a multi-epitope peptide vaccine candidate based on hepatitis C virus NS5A, NS4B and core proteins in HHD-2 mice","volume":"189","author":"Huang","year":"2013","journal-title":"J. Virol. Methods"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1556\/avet.56.2008.3.15","article-title":"Replication and transmission of porcine circovirus type 2 in mice","volume":"56","author":"Cadar","year":"2008","journal-title":"Acta Vet. Hung."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/1743-422X-7-158","article-title":"A mouse model to study infection against porcine circovirus type 2: Viral distribution and lesions in mouse","volume":"7","author":"Li","year":"2010","journal-title":"Virol. J."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Du, Q., Shi, T., Wang, H., Zhu, C., Yang, N., Tong, D., and Huang, Y. (2022). The ultrasonically treated nanoliposomes containing PCV2 DNA vaccine expressing gC1qR binding site mutant Cap is efficient in mice. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.1077026"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"482","DOI":"10.4014\/jmb.1809.09032","article-title":"Comparison of Immune Responses to the PCV2 Replicase-Capsid and Capsid Virus-Like Particle Vaccines in Mice","volume":"29","author":"Jung","year":"2019","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.virusres.2011.11.018","article-title":"Genetic variation of porcine circovirus type 2 (PCV2) and its relevance to vaccination, pathogenesis and diagnosis","volume":"164","author":"Trible","year":"2012","journal-title":"Virus Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2370","DOI":"10.1016\/j.vaccine.2022.03.021","article-title":"A candidate multi-epitope vaccine against porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae induces robust humoral and cellular response in mice","volume":"40","author":"Gao","year":"2022","journal-title":"Vaccine"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/12\/1964\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:58:09Z","timestamp":1760115489000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/12\/1964"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,23]]},"references-count":51,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["v16121964"],"URL":"https:\/\/doi.org\/10.3390\/v16121964","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,23]]}}}