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PCV2 is widely distributed in most developed swine industries, and is a severe economic burden. With an eye to developing an effective, safe, and convenient vaccine against PCV2-associated diseases, we have constructed a recombinant <jats:italic>Bacillus subtilis<\/jats:italic> strain (<jats:italic>B. subtilis<\/jats:italic>-Cap) that expresses the PCV2 capsid protein (Cap).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Electroporation of a plasmid shuttle vector encoding the PCV2 Cap sequence was use to transform <jats:italic>Bacillus subtilis<\/jats:italic>. Flow cytometry was used to evaluate in vitro bone marrow derived dendritic cell (BM-DC) maturation and T cell proliferation induced by <jats:italic>B. subtilis<\/jats:italic>-Cap. Orally inoculated piglets were used for in vivo experiments; ELISA and western blotting were used to evaluate <jats:italic>B. subtilis<\/jats:italic>-Cap induced PCV2-specific IgA and IgG levels, as well as the secretion of cytokines and the expression of Toll-like receptor 2 (TLR2) and Toll-like receptor 9 (TLR9).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We evaluated the immune response to <jats:italic>B. subtilis<\/jats:italic>-Cap in vitro using mouse BM-DCs and in vivo using neonatal piglets orally inoculated with <jats:italic>B. subtilis<\/jats:italic>-Cap. Our results showed that the recombinant <jats:italic>B. subtilis<\/jats:italic>-Cap activated BM-DCs, significantly increased co-stimulatory molecules (CD40 and CD80) and major histocompatibility complex II, and induced allogenic T cells proliferation. Piglets immunized with <jats:italic>B. subtilis<\/jats:italic>-Cap had elevated levels of PCV2-specific IgA in the mucosal tissues of the digestive and respiratory tract, and PCV2-specific IgG in serum (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05 or <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01). Ileal immunocompetent cells, such as the IgA-secreting cells (<jats:italic>P<\/jats:italic>\u00a0&lt;\u20090.01), intestinal intraepithelial lymphocytes (IELs) (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01), CD3<jats:sup>+<\/jats:sup> T lymphocytes (<jats:italic>P<\/jats:italic>\u00a0&lt;\u20090.01) and CD4<jats:sup>+<\/jats:sup> T lymphocytes (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01) increased significantly in the <jats:italic>B. subtilis<\/jats:italic>-Cap immunized piglets. Additionally, <jats:italic>B. subtilis<\/jats:italic>-Cap inoculation resulted in increased the expression of TLR2 and TLR9 (<jats:italic>P<\/jats:italic>\u00a0&lt;\u20090.01), and induced the secretion of cytokines IL-1\u03b2, IL-6, interferon-\u03b3, and \u03b2-defensin 2 (<jats:italic>P<\/jats:italic>\u00a0&lt;\u20090.01).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We constructed a prototype PCV2 vaccine that can be administered orally and elicits a more robust humoral and cellular immunity than inactivated PCV2. <jats:italic>B. subtilis<\/jats:italic>-Cap is a promising vaccine candidate that is safe, convenient, and inexpensive. Further in vivo research is needed to determine its full range of efficacy in pigs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s12964-020-0514-4","type":"journal-article","created":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T17:05:41Z","timestamp":1581440741000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Immune response in piglets orally immunized with recombinant Bacillus subtilis expressing the capsid protein of porcine circovirus type 2"],"prefix":"10.1186","volume":"18","author":[{"given":"Shuai","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunxiao","family":"Mou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"En","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,2,11]]},"reference":[{"key":"514_CR1","doi-asserted-by":"publisher","first-page":"D708","DOI":"10.1093\/nar\/gkx932","volume":"46","author":"EJ Lefkowitz","year":"2018","unstructured":"Lefkowitz EJ, Dempsey DM, Hendrickson RC, Orton RJ, Siddell SG, Smith DB. 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