{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T19:54:09Z","timestamp":1780084449324,"version":"3.54.0"},"reference-count":38,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,2]],"date-time":"2021-10-02T00:00:00Z","timestamp":1633132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades from the Spanish government","award":["RTI2018-100887-B-I00"],"award-info":[{"award-number":["RTI2018-100887-B-I00"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades from the Spanish government","award":["J.A.B. pre-doctoral fellowship FPI 2016"],"award-info":[{"award-number":["J.A.B. pre-doctoral fellowship FPI 2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Classical swine fever virus (CSFV) causes a viral disease of high epidemiological and economical significance that affects domestic and wild swine. Control of the disease in endemic countries is based on live-attenuated vaccines (LAVs) that induce an early protective immune response against highly virulent CSFV strains. The main disadvantage of these currently available LAVs is the lack of serological techniques to differentiate between vaccinated and infected animals (DIVA concept). Here, we describe the development of the FlagDIVA test, a serological diagnostic tool allowing for the differentiation between animals vaccinated with the FlagT4G candidate and those infected with CSFV field strains. The FlagDIVA test is a direct ELISA based on a dendrimeric peptide construct displaying a conserved epitope of CSFV structural protein E2. Although FlagDIVA detected anti-CSFV anti-bodies in infected animals, it did not recognize the antibody response of FlagT4G-vaccinated animals. Therefore, the FlagDIVA test constitutes a valuable accessory DIVA tool in implementing vaccination with the FlagT4G candidate.<\/jats:p>","DOI":"10.3390\/v13101980","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T01:59:47Z","timestamp":1633917587000},"page":"1980","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Development of a Dendrimeric Peptide-Based Approach for the Differentiation of Animals Vaccinated with FlagT4G against Classical Swine Fever from Infected Pigs"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6715-1757","authenticated-orcid":false,"given":"Jos\u00e9 Alejandro","family":"Boh\u00f3rquez","sequence":"first","affiliation":[{"name":"OIE Reference Laboratory for Classical Swine Fever, IRTA-CReSA, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3106-458X","authenticated-orcid":false,"given":"Sira","family":"Defaus","sequence":"additional","affiliation":[{"name":"Departament de Ci\u00e8ncies Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Rosell","sequence":"additional","affiliation":[{"name":"OIE Reference Laboratory for Classical Swine Fever, IRTA-CReSA, 08193 Barcelona, Spain"},{"name":"Departament d\u2019Acci\u00f3 Clim\u00e0tica, Alimentaci\u00f3 i Agenda Rural, Generalitat de Catalunya, 08007 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"P\u00e9rez-Sim\u00f3","sequence":"additional","affiliation":[{"name":"OIE Reference Laboratory for Classical Swine Fever, IRTA-CReSA, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f2nica","family":"Alberch","sequence":"additional","affiliation":[{"name":"OIE Reference Laboratory for Classical Swine Fever, IRTA-CReSA, 08193 Barcelona, Spain"}],"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":"Plum Island Animal Disease Center, Agricultural Research Service, United States Department of Agriculture Greenport, Greenport, NY 11944, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel V.","family":"Borca","sequence":"additional","affiliation":[{"name":"Plum Island Animal Disease Center, Agricultural Research Service, United States Department of Agriculture Greenport, Greenport, NY 11944, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Andreu","sequence":"additional","affiliation":[{"name":"Departament de Ci\u00e8ncies Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8644-3560","authenticated-orcid":false,"given":"Llilianne","family":"Ganges","sequence":"additional","affiliation":[{"name":"OIE Reference Laboratory for Classical Swine Fever, IRTA-CReSA, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,2]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.3201\/eid2506.181578","article-title":"Reemergence of Classical Swine Fever, Japan, 2018","volume":"25","author":"Postel","year":"2019","journal-title":"Emerg. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.vetmic.2017.01.001","article-title":"Classical swine fever vaccines\u2014State-of-the-art","volume":"206","author":"Blome","year":"2017","journal-title":"Vet. Microbiol."},{"key":"ref_4","unstructured":"(2020, February 22). OIE Recognition of the Classical Swine Fever Status of Members; Paris. Available online: https:\/\/www.oie.int\/fileadmin\/Home\/eng\/Animal_Health_in_the_World\/docs\/pdf\/Resolutions\/2019\/A_R22_CSF_status.pdf."},{"key":"ref_5","unstructured":"(2020, March 07). EMA Suvaxyn CSF Marker - EMEA\/V\/C\/002757 - R\/0006. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/veterinary\/EPAR\/suvaxyn-csf-marker."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1080\/22221751.2020.1826893","article-title":"Genetically distinct pestiviruses pave the way to improved classical swine fever marker vaccine candidates based on the chimeric pestivirus concept","volume":"9","author":"Postel","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.virol.2014.09.021","article-title":"Development of an improved live attenuated antigenic marker CSF vaccine strain candidate with an increased genetic stability","volume":"471\u2013473","author":"Holinka","year":"2014","journal-title":"Virology"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Holinka, L.G., O\u2019Donnell, V., Risatti, G.R., Azzinaro, P., Arzt, J., Stenfeldt, C., Velazquez-Salinas, L., Carlson, J., Gladue, D., and Borca, M.V. (2017). Early protection events in swine immunized with an experimental live attenuated classical swine fever marker vaccine, FlagT4G. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177433"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1038\/nbt1088-1204","article-title":"A Short Polypeptide Marker Sequence Useful for Recombinant Protein Identification and Purification","volume":"6","author":"Hopp","year":"1988","journal-title":"Bio\/Technology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1021\/bc900290d","article-title":"Dendrimers for Vaccine and Immunostimulatory Uses. A Review","volume":"21","author":"Heegaard","year":"2010","journal-title":"Bioconjugate Chem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Mhlwatika, Z., and Aderibigbe, B.A. (2018). Application of Dendrimers for the Treatment of Infectious Diseases. Molecules, 23.","DOI":"10.3390\/molecules23092205"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.antiviral.2016.03.005","article-title":"Full protection of swine against foot-and-mouth disease by a bivalent B-cell epitope dendrimer peptide","volume":"129","author":"Blanco","year":"2016","journal-title":"Antivir. Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Forner, M., Ca\u00f1as-Arranz, R., Defaus, S., de Le\u00f3n, P., Rodr\u00edguez-Pulido, M., Ganges, L., Blanco, E., Sobrino, F., and Andreu, D. (2021). Peptide-Based Vaccines: Foot-and-Mouth Disease Virus, a Paradigm in Animal Health. Vaccines, 9.","DOI":"10.3390\/vaccines9050477"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.aca.2012.01.017","article-title":"A dendrimer-based immunosensor for improved capture and detection of tumor necrosis factor-\u03b1 cytokine","volume":"720","author":"Bosnjakovic","year":"2012","journal-title":"Anal. Chim. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.aca.2018.08.038","article-title":"Ultrasensitive ELISA for the detection of hCG based on assembled gold nanoparticles induced by functional polyamidoamine dendrimers","volume":"1042","author":"Wang","year":"2018","journal-title":"Anal. Chim. Acta"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Malvano, F., Pilloton, R., and Albanese, D. (2018). Sensitive Detection of Escherichia coli O157:H7 in Food Products by Impedimetric Immunosensors. Sensors, 18.","DOI":"10.3390\/s18072168"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.vetimm.2012.08.006","article-title":"A T-cell epitope on NS3 non-structural protein enhances the B and T cell responses elicited by dendrimeric constructions against CSFV in domestic pigs","volume":"150","author":"Tarradas","year":"2012","journal-title":"Veter- Immunol. Immunopathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4422","DOI":"10.1016\/j.vaccine.2011.03.095","article-title":"Partial protection against classical swine fever virus elicited by dendrimeric vaccine-candidate peptides in domestic pigs","volume":"29","author":"Tarradas","year":"2011","journal-title":"Vaccine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.virusres.2017.05.020","article-title":"A bivalent dendrimeric peptide bearing a T-cell epitope from foot-and-mouth disease virus protein 3A improves humoral response against classical swine fever virus","volume":"238","author":"Defaus","year":"2017","journal-title":"Virus Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0378-1135(86)90072-6","article-title":"Van Production of monoclonal antibodies against swine fever virus and their use in laboratory diagnosis","volume":"12","author":"Wensvoort","year":"1986","journal-title":"Vet. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","article-title":"A simple method of estimating fifty per cent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Epidemiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0378-1135(84)90026-9","article-title":"The neutralizing peroxidase-linked assay for detection of antibody against swine fever virus","volume":"9","author":"Terpstra","year":"1984","journal-title":"Vet. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sozzi, E., Lavazza, A., Gaffuri, A., Bencetti, F.C., Prosperi, A., Lelli, D., Chiapponi, C., and Moreno, A. (2019). Isolation and Full-Length Sequence Analysis of a Pestivirus from Aborted Lamb Fetuses in Italy. Viruses, 11.","DOI":"10.3390\/v11080744"},{"key":"ref_24","first-page":"1","article-title":"The new emerging ovine pestivirus can infect pigs and confers strong protection against classical swine fever virus","volume":"00","author":"Sozzi","year":"2021","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_25","first-page":"1","article-title":"Investigation of chronic and persistent classical swine fever infections under field conditions and their impact on vaccine efficacy","volume":"15","author":"Coronado","year":"2019","journal-title":"BMC Veter- Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Coronado, L., Perera, C., Rios, L., Fr\u00edas, M., and P\u00e9rez, L. (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_27","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.vetmic.2003.09.008","article-title":"Vaccinology of classical swine fever: From lab to field","volume":"96","year":"2003","journal-title":"Vet. Microbiol."},{"key":"ref_28","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. Veter- Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jviromet.2009.09.012","article-title":"Rational design of a classical swine fever C-strain vaccine virus that enables the differentiation between infected and vaccinated animals","volume":"163","author":"Kortekaas","year":"2010","journal-title":"J. Virol. Methods"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0378-1135(88)90036-3","article-title":"The protective value of vaccine-induced neutralising antibody titres in swine fever","volume":"16","author":"Terpstra","year":"1988","journal-title":"Veter- Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Jelsma, T., Post, J., Born, E., Segers, R., and Kortekaas, J. (2021). Assessing the Protective Dose of a Candidate DIVA Vaccine against Classical Swine Fever. Vaccines, 9.","DOI":"10.3390\/vaccines9050483"},{"key":"ref_32","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_33","doi-asserted-by":"crossref","unstructured":"Wang, M., Sozzi, E., Boh\u00f3rquez, J.A., Alberch, M., Pujols, J., Cantero, G., Gaffuri, A., Lelli, D., Rosell, R., and Bensaid, A. (2020). Decrypting the Origin and Pathogenesis in Pregnant Ewes of a New Ovine Pestivirus Closely Related to Classical Swine Fever Virus. Viruses, 12.","DOI":"10.3390\/v12070775"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s13567-017-0457-y","article-title":"A decade of research into classical swine fever marker vaccine CP7_E2alf (Suvaxyn\u00ae CSF Marker): A review of vaccine properties","volume":"48","author":"Blome","year":"2017","journal-title":"Vet. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1080\/21505594.2021.1959715","article-title":"Abrogation of the RNase activity of Erns in a low virulence classical swine fever virus enhances the humoral immune response and reduces virulence, transmissibility, and persistence in pigs","volume":"12","author":"Wang","year":"2021","journal-title":"Virulence"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.vetmic.2010.05.038","article-title":"Protective efficacy of a Classical swine fever virus C-strain deletion mutant and ability to differentiate infected from vaccinated animals","volume":"147","author":"Kortekaas","year":"2011","journal-title":"Vet. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jim.2015.03.009","article-title":"Discrimination within epitope specific antibody populations against Classical swine fever virus is a new means of differentiating infection from vaccination","volume":"420","author":"Bruderer","year":"2015","journal-title":"J. Immunol. Methods"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1111\/tbed.13293","article-title":"Positive selection pressure on E2 protein of classical swine fever virus drives variations in virulence, pathogenesis and antigenicity: Implication for epidemiological surveillance in endemic areas","volume":"66","author":"Coronado","year":"2019","journal-title":"Transbound. Emerg. Dis."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/10\/1980\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:08:44Z","timestamp":1760166524000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/10\/1980"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,2]]},"references-count":38,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["v13101980"],"URL":"https:\/\/doi.org\/10.3390\/v13101980","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,2]]}}}