{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:51:09Z","timestamp":1787579469256,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T00:00:00Z","timestamp":1638748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Program on Key Research Project of China","award":["2021YFD1800003"],"award-info":[{"award-number":["2021YFD1800003"]}]},{"name":"National Program on Key Research Project of China","award":["2018YFD0500801"],"award-info":[{"award-number":["2018YFD0500801"]}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2662016PY003"],"award-info":[{"award-number":["2662016PY003"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Congenital tremor (CT) type A-II in piglets is caused by an emerging atypical porcine pestivirus (APPV), which is prevalent in swine herds and a serious threat to the pig production industry. This study aimed to construct APPV E2 subunit vaccines fused with Fc fragments and evaluate their immunogenicity in piglets. Here, APPV E2Fc and E2\u0394Fc fusion proteins expressed in Drosophila Schneider 2 (S2) cells were demonstrated to form stable dimers in SDS-PAGE and western blotting assays. Functional analysis revealed that aE2Fc and aE2\u0394Fc fusion proteins could bind to Fc\u03b3RI on antigen-presenting cells (APCs), with the affinity of aE2Fc to Fc\u03b3RI being higher than that of aE2\u0394Fc. Moreover, subunit vaccines based on aE2, aE2Fc, and aE2\u0394Fc fusion proteins were prepared, and their immunogenicity was evaluated in piglets. The results showed that the Fc fusion proteins emulsified with the ISA 201VG adjuvant elicited stronger humoral and cellular immune responses than the IMS 1313VG adjuvant. These findings suggest that APPV E2 subunit vaccines fused with Fc fragments may be a promising vaccine candidate against APPV.<\/jats:p>","DOI":"10.3390\/v13122443","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T03:21:05Z","timestamp":1638847265000},"page":"2443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Fc-Mediated E2-Dimer Subunit Vaccines of Atypical Porcine Pestivirus Induce Efficient Humoral and Cellular Immune Responses in Piglets"],"prefix":"10.3390","volume":"13","author":[{"given":"Xujiao","family":"Ren","sequence":"first","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Qian","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shudan","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanchun","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangmin","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,6]]},"reference":[{"key":"ref_1","first-page":"123","article-title":"Dancing pigs?","volume":"17","author":"Kinsley","year":"1922","journal-title":"Vet. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Arruda, B.L., Arruda, P.H., Magstadt, D.R., Schwartz, K.J., Dohlman, T., Schleining, J.A., Patterson, A.R., Visek, C.A., and Victoria, J.G. (2016). Identification of a Divergent Lineage Porcine Pestivirus in Nursing Piglets with Congenital Tremors and Reproduction of Disease following Experimental Inoculation. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150104"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"De Groof, A., Deijs, M., Guelen, L., van Grinsven, L., van Os-Galdos, L., Vogels, W., Derks, C., Cruijsen, T., Geurts, V., and Vrijenhoek, M. (2016). Atypical Porcine Pestivirus: A Possible Cause of Congenital Tremor Type A-II in Newborn Piglets. Viruses, 8.","DOI":"10.3390\/v8100271"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"27735","DOI":"10.1038\/srep27735","article-title":"Presence of atypical porcine pestivirus (APPV) genomes in newborn piglets correlates with congenital tremor","volume":"6","author":"Postel","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13028-014-0082-y","article-title":"Astrovirus as a possible cause of congenital tremor type AII in piglets?","volume":"56","author":"Ley","year":"2014","journal-title":"Acta Vet. Scand."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/tbed.12807","article-title":"Viruses associated with congenital tremor and high lethality in piglets","volume":"65","author":"Possatti","year":"2018","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13567-016-0406-1","article-title":"Congenital infection with atypical porcine pestivirus (APPV) is associated with disease and viral persistence","volume":"48","author":"Schwarz","year":"2017","journal-title":"Vet. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e501","DOI":"10.1111\/tbed.12772","article-title":"Evidence of porcine circovirus-like virus P1 in piglets with an unusual congenital tremor","volume":"65","author":"Wen","year":"2018","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1099\/jgv.0.000251","article-title":"Discovery of a novel putative atypical porcine pestivirus in pigs in the USA","volume":"96","author":"Hause","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"11872","DOI":"10.1128\/JVI.00754-13","article-title":"Autocatalytic cleavage within classical swine fever virus NS3 leads to a functional separation of protease and helicase","volume":"87","author":"Lamp","year":"2013","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e2018","DOI":"10.1002\/rmv.2018","article-title":"An emerging novel virus: Atypical porcine pestivirus (APPV)","volume":"29","author":"Pan","year":"2019","journal-title":"Rev. Med. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7088","DOI":"10.1128\/jvi.67.12.7088-7095.1993","article-title":"Processing of pestivirus polyprotein: Cleavage site between autoprotease and nucleocapsid protein of classical swine fever virus","volume":"67","author":"Stark","year":"1993","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/bs.aivir.2015.03.002","article-title":"The Molecular Biology of Pestiviruses","volume":"93","author":"Tautz","year":"2015","journal-title":"Adv. Virus. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zhang, H., Wen, W., Hao, G., Chen, H., Qian, P., and Li, X. (2018). A Subunit Vaccine Based on E2 Protein of Atypical Porcine Pestivirus Induces Th2-type Immune Response in Mice. Viruses, 10.","DOI":"10.3390\/v10120673"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2733","DOI":"10.1007\/s00705-021-05185-w","article-title":"Vaccination with virus-like particles of atypical porcine pestivirus inhibits virus replication in tissues of BALB\/c mice","volume":"166","author":"Liu","year":"2021","journal-title":"Arch. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4574","DOI":"10.1016\/j.vaccine.2020.05.013","article-title":"Efficient mucosal vaccination of a novel classical swine fever virus E2-Fc fusion protein mediated by neonatal Fc receptor","volume":"38","author":"Li","year":"2020","journal-title":"Vaccine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"862","DOI":"10.3389\/fmicb.2017.00862","article-title":"Atypical Porcine Pestivirus as a Novel Type of Pestivirus in Pigs in China","volume":"8","author":"Yuan","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/tbed.13029","article-title":"Molecular characterization of two novel atypical porcine pestivirus (APPV) strains from piglets with congenital tremor in China","volume":"66","author":"Pan","year":"2019","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.virol.2019.04.010","article-title":"12 novel atypical porcine pestivirus genomes from neonatal piglets with congenital tremors: A newly emerging branch and high prevalence in China","volume":"533","author":"Yan","year":"2019","journal-title":"Virology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.3389\/fmicb.2019.01406","article-title":"Detection and Genetic Characterization of Atypical Porcine Pestivirus in Piglets with Congenital Tremors in Southern China","volume":"10","author":"Xie","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1080\/19420862.2019.1633883","article-title":"Antibody Fc engineering for enhanced neonatal Fc receptor binding and prolonged circulation half-life","volume":"11","author":"Mackness","year":"2019","journal-title":"MAbs"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"25154","DOI":"10.1074\/jbc.M113.484154","article-title":"Engineered soluble monomeric IgG1 CH3 domain: Generation, mechanisms of function, and implications for design of biological therapeutics","volume":"288","author":"Ying","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"19399","DOI":"10.1074\/jbc.M112.368647","article-title":"Soluble monomeric IgG1 Fc","volume":"287","author":"Ying","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"269","DOI":"10.3109\/1061186X.2013.875030","article-title":"Neonatal Fc receptor (FcRn): A novel target for therapeutic antibodies and antibody engineering","volume":"22","author":"Wang","year":"2014","journal-title":"J. Drug. Target."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1007\/s00705-019-04345-3","article-title":"Viral load and histological distribution of atypical porcine pestivirus in different tissues of naturally infected piglets","volume":"164","author":"Liu","year":"2019","journal-title":"Arch. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Cagatay, G.N., Meyer, D., Wendt, M., Becher, P., and Postel, A. (2019). Characterization of the Humoral Immune Response Induced after Infection with Atypical Porcine Pestivirus (APPV). Viruses, 11.","DOI":"10.3390\/v11100880"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1111\/tbed.12659","article-title":"Identification of atypical porcine pestivirus infection in swine herds in China","volume":"64","author":"Zhang","year":"2017","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e202","DOI":"10.1111\/tbed.12675","article-title":"Phylogenetic and genomic characterization of a novel atypical porcine pestivirus in China","volume":"65","author":"Zhang","year":"2018","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.virol.2004.09.023","article-title":"Characterization of classical swine fever virus entry by using pseudotyped viruses: E1 and E2 are sufficient to mediate viral entry","volume":"330","author":"Wang","year":"2004","journal-title":"Virology"},{"key":"ref_30","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_31","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_32","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.4049\/jimmunol.0903296","article-title":"Importance of neonatal FcR in regulating the serum half-life of therapeutic proteins containing the Fc domain of human IgG1: A comparative study of the affinity of monoclonal antibodies and Fc-fusion proteins to human neonatal FcR","volume":"184","author":"Suzuki","year":"2010","journal-title":"J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1080\/19420862.2015.1008353","article-title":"The neonatal Fc receptor (FcRn) binds independently to both sites of the IgG homodimer with identical affinity","volume":"7","author":"Abdiche","year":"2015","journal-title":"MAbs"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1002\/emmm.201201379","article-title":"Fc-fusion proteins: New developments and future perspectives","volume":"4","author":"Czajkowsky","year":"2012","journal-title":"EMBO Mol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1080\/22221751.2020.1743767","article-title":"Establishment and validation of a pseudovirus neutralization assay for SARS-CoV-2","volume":"9","author":"Nie","year":"2020","journal-title":"Emerg. Microbes. Infect."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1080\/22221751.2020.1815589","article-title":"Robust neutralization assay based on SARS-CoV-2 S-protein-bearing vesicular stomatitis virus (VSV) pseudovirus and ACE2-overexpressing BHK21 cells","volume":"9","author":"Xiong","year":"2020","journal-title":"Emerg. Microbes. Infect."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e20201181","DOI":"10.1084\/jem.20201181","article-title":"Measuring SARS-CoV-2 neutralizing antibody activity using pseudotyped and chimeric viruses","volume":"217","author":"Schmidt","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"105282","DOI":"10.1016\/j.micpath.2021.105282","article-title":"Genetic characterization of atypical porcine pestivirus (APPV) in China and the successful isolation of a novel APPV strain within genotype 2","volume":"161","author":"Zhang","year":"2021","journal-title":"Microb. Pathog."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/12\/2443\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:40:04Z","timestamp":1760168404000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/12\/2443"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,6]]},"references-count":38,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["v13122443"],"URL":"https:\/\/doi.org\/10.3390\/v13122443","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,6]]}}}