{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T08:59:02Z","timestamp":1793350742798,"version":"4.5.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p><jats:italic>Chlamydia trachomatis<\/jats:italic> (CT) is a major sexually transmitted pathogen with severe complications. Using <jats:italic>Chlamydia muridarum<\/jats:italic> (CM) as a model, this study evaluates the attenuated mutant <jats:italic>Chlamydia muridarum<\/jats:italic> (CM-pGP3S) as a novel rectal vaccine to protect against genital tract infection and pathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Female C57BL\/6 mice were rectally immunized with low (1\u00d710<jats:sup>3<\/jats:sup>), middle (1\u00d710<jats:sup>5<\/jats:sup>), or high (1\u00d710<jats:sup>7<\/jats:sup>) doses of CM-pGP3S. Mice were challenged intravaginally with wild-type <jats:italic>Chlamydia muridarum<\/jats:italic> 63 days post-immunization. Protection was assessed via genital <jats:italic>Chlamydia<\/jats:italic> shedding, hydrosalpinx incidence (gross\/histopathology), serum IgG, fecal IgA, and T cell responses. Gut microbiota stability was analyzed using qPCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CM-pGP3S immunization significantly reduced CM-WT genital shedding duration (3\u20137 days vs. 21 days in controls, <jats:italic>p<\/jats:italic> &amp;lt; 0.01) and hydrosalpinx incidence (0% vs. 80% in controls, <jats:italic>p<\/jats:italic> &amp;lt; 0.01). Elevated systemic and mucosal immunity were observed, including higher serum IgG (1:100\u20131:1600 dilutions, <jats:italic>p<\/jats:italic>\u00a0&amp;lt; 0.05\u20130.01) and fecal IgA (<jats:italic>p<\/jats:italic> &amp;lt; 0.05\u20130.01). CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells exhibited increased IFN-\u03b3 (<jats:italic>p<\/jats:italic> &amp;lt; 0.01), while CD8<jats:sup>+<\/jats:sup> T cells showed elevated TNF-\u03b1 and IL-2 (<jats:italic>p<\/jats:italic>\u00a0&amp;lt; 0.05). No colitis or significant gut microbiota disruption occurred post-immunization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Rectal CM-pGP3S vaccination induces robust transmucosal immunity, protecting against genital <jats:italic>Chlamydia <\/jats:italic>infection and pathology without gastrointestinal adverse effects. This highlights its potential as a safe and effective mucosal vaccine strategy to combat CT genital tract infections.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1550455","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T05:30:46Z","timestamp":1747114246000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Chlamydia muridarum mutant CM-pGP3S as a novel attenuated live rectal vaccine protects against genital tract infection"],"prefix":"10.3389","volume":"15","author":[{"given":"Jingyue","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanzhong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangming","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanjun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1093\/intimm\/dxu063","article-title":"Challenges in mucosal vaccines for the control of infectious diseases","volume":"26","author":"Azegami","year":"2014","journal-title":"Int. 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