https://phaidra.vetmeduni.ac.at/o:5594 A Chlamydia trachomatis CPAF-STING agonist conjugate vaccine administered intramuscularly and intradermally is immunogenic in the pig model Bettin, Leonie Leonie Bettin University of Veterinary Medicine Vienna. Centre of Pathobiology Unterweger, Christine Christine Unterweger 0000-0003-4965-2088 University of Veterinary Medicine Vienna. Clinical Centre for Population Medicine in Fish, Pig and Poultry Dippel, Maximiliane Maximiliane Dippel 0000-0001-7016-5853 University of Veterinary Medicine Vienna. Clinical Centre for Population Medicine in Fish, Pig and Poultry Borysova, Tamara Tamara Borysova University of Veterinary Medicine Vienna. Centre of Pathobiology Stadler, Maria Maria Stadler University of Veterinary Medicine Vienna. Centre of Pathobiology Harris, Jonathan Jonathan Harris Rozzelle, James James Rozzelle Arroyo, Daisy Daisy Arroyo , Inc. Fairman, Jeff Jeff Fairman Poston, Taylor B. Taylor B. Poston Perouzel, Eric Eric Perouzel Lioux, Thierry Thierry Lioux Hernandez-Franco, Juan F. Juan F. Hernandez-Franco Hogen Esch, Harm Harm Hogen Esch Buzanich-Ladinig, Andrea Andrea Buzanich-Ladinig 0000-0001-5037-7269 University of Veterinary Medicine Vienna. Clinical Centre for Population Medicine in Fish, Pig and Poultry Darville, Toni Toni Darville Käser, Tobias Tobias Käser 0000-0001-8764-7971 University of Veterinary Medicine Vienna. Centre of Pathobiology Frontiers Media SA journal article open access eng Introduction: Chlamydia trachomatis (Ct) is the most common bacterial cause of sexually transmitted infection worldwide. Given the limited effectiveness of current Ct screening and treatment programs, alongside the lack of lasting immunity from natural infection, developing an effective vaccine is crucial. Pigs serve as a valuable model for chlamydia research due to their physiological similarity to humans and natural susceptibility to Chlamydia suis (Cs), a close relative of Ct. Thus, we utilized the pig model to evaluate the immunogenicity of three Chlamydial Protease-like Activity Factor (CPAF)-based vaccine candidates. Because stimulator of interferon genes (STING) pathway agonists have shown promise as adjuvants for subunit vaccines but are limited by rapid diffusion from the injection site and poor cellular uptake, we evaluated two improved STING agonist formulations: direct conjugation of the agonist to CPAF (CPAF-STG1151) and adsorption onto phytoglycogen nanoparticles (CPAF/NanoST), and compared their performance to a conventional oil-in-water microemulsion adjuvant (CPAF/IMS1313). Methods: Pigs received two intramuscular (IM) or two intradermal (ID) doses and adaptive immune responses were assessed weekly by three-color FluoroSpot assays, multi-parameter flow cytometry and anti-CPAF ELISAs. Results: Among the vaccine candidates tested, the novel CPAF-STG1151 conjugate elicited the strongest systemic T cell response. It induced a robust cell-mediated immune response characterized by IFNγ production with or without TNFα coproduction and this response was equally mediated by all T cell subsets (CD4, CD8 and γδ T cells). The route of administration (IM vs. ID) had no significant effect on either the magnitude or the cytokine profile of the cell-mediated immune response. The highest anti-CPAF IgG serum levels were also observed following vaccination with the CPAF-STG1151 conjugate vaccine candidate. Discussion: Thus, conjugation of the STING pathway agonist STG1151 to the Chlamydia protein CPAF resulted in a highly immunogenic subunit vaccine. Future studies will determine mucosal administration routes and assess the vaccine efficacy of this promising Ct vaccine candidate. Chlamydia trachomatis conjugate vaccine CPAF pig STING agonist swine http://creativecommons.org/licenses/by/4.0/ https://phaidra.vetmeduni.ac.at/api/object/o:5594/download 10.3389/fimmu.2026.1816737 https://phaidra.vetmeduni.ac.at/o:605 application/pdf Frontiers in Immunology issn:1664-3224 VoR Frontiers in Immunology 17 5.46 MB 2026