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Attempts to control this epidemic with screening programs and antibiotic therapy have failed. Currently, a vaccine to prevent<jats:named-content content-type=\"genus-species\">C. trachomatis<\/jats:named-content>infections is not available. In order to develop an animal model for evaluating vaccine antigens that can be applied to humans, we used<jats:named-content content-type=\"genus-species\">C. trachomatis<\/jats:named-content>serovar D (strain UW-3\/Cx) to induce infertility in mice whose major histocompatibility complex class II antigen was replaced with the human leukocyte antigen DR4 (HLA-DR4). Transcervical inoculation of medroxyprogesterone-treated HLA-DR4 transgenic mice with 5 \u00d7 10<jats:sup>5<\/jats:sup><jats:named-content content-type=\"genus-species\">C. trachomatis<\/jats:named-content>D inclusion forming units (IFU) induced a significant reduction in fertility, with a mean number of embryos\/mouse of 4.4 \u00b1 1.3 compared to 7.8 \u00b1 0.5 for the uninfected control mice (<jats:italic>P<\/jats:italic>&lt; 0.05). A similar fertility reduction was elicited in the wild-type (WT) C57BL\/6 mice (4.3 \u00b1 1.4 embryos\/mouse) compared to the levels of the WT controls (9.1 \u00b1 0.4 embryos\/mouse) (<jats:italic>P<\/jats:italic>&lt; 0.05). Following infection, WT mice mounted more robust humoral and cellular immune responses than HLA-DR4 mice. As determined by vaginal shedding, HLA-DR4 mice were more susceptible to a transcervical<jats:named-content content-type=\"genus-species\">C. trachomatis<\/jats:named-content>D infection than WT mice. To assess if HLA-DR4 transgenic and WT mice could be protected by vaccination, 10<jats:sup>4<\/jats:sup>IFU of<jats:named-content content-type=\"genus-species\">C. trachomatis<\/jats:named-content>D was delivered intranasally, and mice were challenged transcervically 6 weeks later with 5 \u00d7 10<jats:sup>5<\/jats:sup>IFU of<jats:named-content content-type=\"genus-species\">C. trachomatis<\/jats:named-content>D. As determined by severity and length of vaginal shedding, WT C57BL\/6 and HLA-DR4 mice were significantly protected by vaccination. The advantages and limitations of the HLA-DR4 transgenic mouse model for evaluating human<jats:named-content content-type=\"genus-species\">C. trachomatis<\/jats:named-content>vaccine antigens are discussed.<\/jats:p>","DOI":"10.1128\/iai.00722-17","type":"journal-article","created":{"date-parts":[[2017,10,17]],"date-time":"2017-10-17T00:55:25Z","timestamp":1508201725000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["Transcervical Inoculation with Chlamydia trachomatis Induces Infertility in HLA-DR4 Transgenic and Wild-Type Mice"],"prefix":"10.1128","volume":"86","author":[{"given":"Sukumar","family":"Pal","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delia F.","family":"Tifrea","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangming","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis M.","family":"de la Maza","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Chlamydial infections","author":"Centers for Disease Control and Prevention","year":"2015","unstructured":"Centers for Disease Control and Prevention. 2015. 2015 Sexually transmitted diseases treatment guidelines. 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