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In this study, we investigated the role of C. perfringens sporulation proteins as vaccine candidates in chickens to reduce necrotic enteritis (NE). C. perfringens soluble proteins of vegetative cells (CP-super1 and CP-super2) and spores (CP-spor-super1 and CP-spor-super2) were prepared, and cell and chicken experiments were conducted. We found that deoxycholic acid reduced C. perfringens invasion and sporulation using the Eimeria maxima and C. perfringens co-infection necrotic enteritis (NE) model. C. perfringens enterotoxin (CPE) was detected in the CP-spor-super1&amp;2. CP-spor-super1 or 2 induced cell death in mouse epithelial CMT-93 and macrophage Raw 264.7 cells. CP-spor-super1 or 2 also induced inflammatory gene expression and necrosis in the Raw cells. Birds immunized with CP-spor-super1 or 2 were resistant to C. perfringens-induced severe clinical NE on histopathology and body weight gain loss. CP-spor-super1 vaccine reduced NE-induced proinflammatory Ifn\u03b3 gene expression as well as C. perfringens luminal colonization and tissue invasion in the small intestine. Together, this study showed that CP-spor-super vaccines reduced NE histopathology and productivity loss.<\/jats:p>","DOI":"10.3390\/microorganisms10061110","type":"journal-article","created":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T23:43:03Z","timestamp":1653867783000},"page":"1110","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Vaccines Using Clostridium perfringens Sporulation Proteins Reduce Necrotic Enteritis in Chickens"],"prefix":"10.3390","volume":"10","author":[{"given":"Ying","family":"Fu","sequence":"first","affiliation":[{"name":"Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA"},{"name":"Cell and Molecular Biology (CEMB), University of Arkansas, Fayetteville, AR 72701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohit","family":"Bansal","sequence":"additional","affiliation":[{"name":"Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tahrir","family":"Alenezi","sequence":"additional","affiliation":[{"name":"Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA"},{"name":"Cell and Molecular Biology (CEMB), University of Arkansas, Fayetteville, AR 72701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayidh","family":"Almansour","sequence":"additional","affiliation":[{"name":"Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA"},{"name":"Cell and Molecular Biology (CEMB), University of Arkansas, Fayetteville, AR 72701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5601-0812","authenticated-orcid":false,"given":"Xiaolun","family":"Sun","sequence":"additional","affiliation":[{"name":"Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA"},{"name":"Cell and Molecular Biology (CEMB), University of Arkansas, Fayetteville, AR 72701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41426-018-0144-8","article-title":"An update on the human and animal enteric pathogen Clostridium perfringens","volume":"7","author":"Kiu","year":"2018","journal-title":"Emerg. 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