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In this study, we developed a novel competitive enzyme-linked immunosorbent assay (cELISA) based on a C-strain Erns specific monoclonal antibody (mAb 1504), aiming to serologically measure immune responses to C-strain vaccine in pigs, and finally to make the C-strain become a DIVA-compatible vaccine. The cELISA system was established based on the strategy that mAb 1504 will compete with the C-strain induced antibodies in the pig serum to bind the C-strain Erns protein. The cELISA was optimized and was further evaluated by testing different categories of pig sera. It can efficiently differentiate C-strain immunized from wild-type CSFV-infected pigs and lacks cross-reaction with other common swine viruses and viruses in genus Pestivirus such as Bovine viral diarrhea virus (BVDV). The C-strain antibody can be tested in pigs 7\u201314 days post vaccination with this cELISA. The sensitivity and specificity of the established cELISA were 100% (95% confidence interval: 95.60 to 100%) and 100% (95% confidence interval: 98.30 to 100%), respectively. This novel cELISA is a reliable tool for specifically measuring and differentiating immune responses to C-strain vaccine in pigs. By combining with the wild-type CSFV-specific infection tests, it can make the C-strain have DIVA capability.<\/jats:p>","DOI":"10.3390\/v14071544","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T01:53:22Z","timestamp":1658109202000},"page":"1544","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Novel Competitive ELISA for Specifically Measuring and Differentiating Immune Responses to Classical Swine Fever C-Strain Vaccine in Pigs"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7951-4175","authenticated-orcid":false,"given":"Lihua","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shijiang","family":"Mi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Zoonoses Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130012, China"},{"name":"Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Madera","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuzhen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjie","family":"Gong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Zoonoses Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changchun","family":"Tu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Zoonoses Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130012, China"},{"name":"Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7177-9280","authenticated-orcid":false,"given":"Jishu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0378-1135(00)00137-1","article-title":"Introduction to classical swine fever: Virus, disease and control policy","volume":"73","author":"Moennig","year":"2000","journal-title":"Vet. 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