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Up to now, few efficient vaccines against<jats:italic>E. mitis<\/jats:italic>have been reported, whereas the recombinant subunit vaccines delivered by nanomaterials may elicit an encouraging outcome. Thus, in this study, we chose<jats:italic>E. mitis<\/jats:italic>1a (Em1a) protein as the candidate antigen to generate Em1a preparations. The recombinant Em1a (rEm1a) protein was encapsulated with poly lactic-co-glycolic acid (PLGA) and chitosan (CS) nanospheres. The physical characterization of the rEm1a-PLGA and rEm1a-CS nanospheres was investigated, and the resulting nanospheres were proven to be nontoxic. The protective efficacy of rEm1a-PLGA and rEm1a-CS preparations was evaluated in<jats:italic>E. mitis<\/jats:italic>-challenged birds in comparison with two preparations containing rEm1a antigen emulsified in commercially available adjuvants. ELISA assay, flow cytometry analysis, and quantitative real-time PCR (qPCR) analysis indicated that vaccination with rEm1a-loaded nanospheres significantly upregulated the secretions of antibodies and cytokines and proportions of CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T lymphocytes. Compared with the other three preparations, rEm1a-PLGA nanosphere was more effective in improving growth performance and inhibiting oocyst output in feces, indicating that the PLGA nanosphere was associated with optimal protection against<jats:italic>E. mitis<\/jats:italic>. Collectively, our results highlighted the advantages of nanovaccine in eliciting protective immunity and may provide a new perspective for developing effective vaccines against chicken coccidiosis.<\/jats:p>","DOI":"10.3389\/fimmu.2022.901758","type":"journal-article","created":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T07:27:58Z","timestamp":1653550078000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["PLGA Nanospheres as Delivery Platforms for Eimeria mitis 1a Protein: A Novel Strategy to Improve Specific Immunity"],"prefix":"10.3389","volume":"13","author":[{"given":"Lixin","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengqing","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaohai","family":"Wen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Tahir","family":"Aleem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruofeng","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaokai","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingmin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"XiangRui","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1186\/s13567-020-00837-2","article-title":"Re-Calculating the Cost of Coccidiosis in Chickens","volume":"51","author":"Blake","year":"2020","journal-title":"Veterin. 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