{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T11:57:21Z","timestamp":1793361441401,"version":"4.5.0"},"reference-count":50,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI162709"],"award-info":[{"award-number":["R01AI162709"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Veterinary Medicine Vienna","award":["R01AI162709"],"award-info":[{"award-number":["R01AI162709"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Chlamydia trachomatis (Ct) infections are the most common sexually transmitted infection (STI). Despite effective antibiotics for Ct, undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as C. suis (Cs) in pigs. Based on the similarities between humans and pigs, as well as their chlamydia species, we use pigs as a large biomedical animal model for chlamydia research. In this study, we used the pig model to develop a vaccine candidate against Ct. The vaccine candidate consists of TriAdj-adjuvanted chlamydial-protease-like activity factor (CPAF) protein. We tested two weekly administration options\u2014twice intranasal (IN) followed by twice intramuscular (IM) and twice IM followed by twice IN. We assessed the humoral immune response in both serum using CPAF-specific IgG (including antibody avidity determination) and also in cervical and rectal swabs using CPAF-specific IgG and IgA ELISAs. The systemic T-cell response was analyzed following in vitro CPAF restimulation via IFN-\u03b3 and IL-17 ELISpots, as well as intracellular cytokine staining flow cytometry. Our data demonstrate that while the IN\/IM vaccination mainly led to non-significant systemic immune responses, the vaccine candidate is highly immunogenic if administered IM\/IN. This vaccination strategy induced high serum anti-CPAF IgG levels with strong avidity, as well as high IgA and IgG levels in vaginal and rectal swabs and in uterine horn flushes. In addition, this vaccination strategy prompted a pronounced cellular immune response. Besides inducing IL-17 production, the vaccine candidate induced a strong IFN-\u03b3 response with CD4 T cells. In IM\/IN-vaccinated pigs, these cells also significantly downregulated their CCR7 expression, a sign of differentiation into peripheral-tissue-homing effector\/memory cells. Conclusively, this study demonstrates the strong immunogenicity of the IM\/IN-administered TriAdj-adjuvanted Ct CPAF vaccine candidate. Future studies will test the vaccine efficacy of this promising Ct vaccine candidate. In addition, this project demonstrates the suitability of the Cs pre-exposed outbred pig model for Ct vaccine development. Thereby, we aim to open the bottleneck of large animal models to facilitate the progression of Ct vaccine candidates into clinical trials.<\/jats:p>","DOI":"10.3390\/vaccines12040423","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T08:41:06Z","timestamp":1713256866000},"page":"423","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A TriAdj-Adjuvanted Chlamydia trachomatis CPAF Protein Vaccine Is Highly Immunogenic in Pigs"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7835-6096","authenticated-orcid":false,"given":"Jessica","family":"Proctor","sequence":"first","affiliation":[{"name":"Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Stadler","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Pathobiology, Center of Pathobiology, Immunology, University of Veterinary Medicine Vienna, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizette M.","family":"Cortes","sequence":"additional","affiliation":[{"name":"Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Brodsky","sequence":"additional","affiliation":[{"name":"Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Poisson","sequence":"additional","affiliation":[{"name":"Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Gerdts","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK S7N 5A3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex I.","family":"Smirnov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, North Carolina State University, Raleigh, NC 27607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana I.","family":"Smirnova","sequence":"additional","affiliation":[{"name":"Department of Chemistry, North Carolina State University, Raleigh, NC 27607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6441-8930","authenticated-orcid":false,"given":"Subarna","family":"Barua","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Leahy","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Infection Control, Queensland University of Technology, Brisbane 4000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth W.","family":"Beagley","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Infection Control, Queensland University of Technology, Brisbane 4000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Harris","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Infection Control, Queensland University of Technology, Brisbane 4000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni","family":"Darville","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of North Carolina, Chapel Hill, NC 27514, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8764-7971","authenticated-orcid":false,"given":"Tobias","family":"K\u00e4ser","sequence":"additional","affiliation":[{"name":"Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA"},{"name":"Department of Biological Sciences and Pathobiology, Center of Pathobiology, Immunology, University of Veterinary Medicine Vienna, 1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a010256","DOI":"10.1101\/cshperspect.a010256","article-title":"Chlamydial Intracellular Survival Strategies","volume":"3","author":"Bastidas","year":"2013","journal-title":"Cold Spring Harb. 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