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The present study investigated local and systemic humoral and cell-mediated immune responses and efficacy upon vaccination of piglets with a combined vaccine containing inactivated\n                    <jats:italic>M. hyopneumoniae<\/jats:italic>\n                    and porcine circovirus 2d (Cirbloc\n                    <jats:sup>\u00ae<\/jats:sup>\n                    M Hyo, Ceva), followed by experimental\n                    <jats:italic>M. hyopneumoniae<\/jats:italic>\n                    infection (D21). Forty-five piglets were allocated to three groups, namely the not-vaccinated and infected (C) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200920), vaccinated and infected (V) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200920), and not-vaccinated and not-infected (NC) groups (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20095). Vaccination was applied once (D0) intramuscularly. Four pigs from the V and C groups were euthanized 2\u00a0weeks post-infection (D35), and the remaining pigs 2\u00a0weeks later (D49). Blood, lung tissue, bronchoalveolar lavage fluid (BALF), and bronchial lymph nodes were collected at different timepoints. Piglets in the V group exhibited seroconversion on days 21 and 35, with markedly elevated levels of specific IgA and IgG in BALF on D35. Furthermore, the V group showed activation of interferon (IFN)-\u03b3\n                    <jats:sup>+<\/jats:sup>\n                    \/tumor necrosis factor (TNF)-\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD8\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    T cells and T cell proliferation on day 7, with these responses remaining elevated through D21. The concentrations of interleukin (IL)-1\u03b2, TNF-\u03b1, C\u2013X\u2013C motif chemokine ligand 8 (CXCL-8), and IL-17A in BALF of the C group were higher on D49, correlating with higher\n                    <jats:italic>M. hyopneumoniae<\/jats:italic>\n                    DNA loads. Clinical signs and lung lesions were less severe in vaccinated pigs. The combined vaccine elicited robust\n                    <jats:italic>M. hyopneumoniae<\/jats:italic>\n                    -specific humoral and cellular responses in blood and enhanced post-infection cellular immunity in draining lymph nodes, underscoring its protective efficacy.\n                  <\/jats:p>","DOI":"10.1186\/s13567-026-01808-9","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T09:17:48Z","timestamp":1783415868000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunogenicity and efficacy of a Mycoplasma hyopneumoniae\/porcine circovirus type 2 combination vaccine against experimental Mycoplasma hyopneumoniae infection in pigs"],"prefix":"10.1186","volume":"57","author":[{"given":"Li","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Van Immerseel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilias","family":"Chantziaras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Sonalio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Karolina","family":"Panneitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Krejci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominiek","family":"Maes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert","family":"Devriendt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"issue":"Suppl 1","key":"1808_CR1","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1111\/tbed.12677","volume":"65","author":"D Maes","year":"2018","unstructured":"Maes D, Sibila M, Kuhnert P, Segal\u00e9s J, Haesebrouck F, Pieters M (2018) Update on Mycoplasma hyopneumoniae infections in pigs: Knowledge gaps for improved disease control. 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