Leonie Bettin (Centre of Pathobiology, Department of Biological Sciences and Pathobiology, Departments, University of Veterinary Medicine Vienna) Leonie Bettin Christine Unterweger (Clinical Centre for Population Medicine in Fish, Pig and Poultry, Clinical Department for Farm Animals and Food System Transformation, Departments, University of Veterinary Medicine Vienna) Christine Unterweger Maximiliane Dippel (Clinical Centre for Population Medicine in Fish, Pig and Poultry, Clinical Department for Farm Animals and Food System Transformation, Departments, University of Veterinary Medicine Vienna) Maximiliane Dippel Tamara Borysova (Centre of Pathobiology, Department of Biological Sciences and Pathobiology, Departments, University of Veterinary Medicine Vienna) Tamara Borysova Maria Stadler (Centre of Pathobiology, Department of Biological Sciences and Pathobiology, Departments, University of Veterinary Medicine Vienna) Maria Stadler Jonathan Harris Jonathan Harris James Rozzelle James Rozzelle Daisy Arroyo (, Inc.) Daisy Arroyo Jeff Fairman Jeff Fairman Taylor B. Poston Taylor B. Poston Eric Perouzel Eric Perouzel Thierry Lioux Thierry Lioux Juan F. Hernandez-Franco Juan F. Hernandez-Franco Harm Hogen Esch Harm Hogen Esch Andrea Buzanich-Ladinig (Clinical Centre for Population Medicine in Fish, Pig and Poultry, Clinical Department for Farm Animals and Food System Transformation, Departments, University of Veterinary Medicine Vienna) Andrea Buzanich-Ladinig Toni Darville Toni Darville Tobias Käser (Centre of Pathobiology, Department of Biological Sciences and Pathobiology, Departments, University of Veterinary Medicine Vienna) Tobias Käser Frontiers Media SA 2026 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. PDFDocument eng 2026-10-14T08:03:18.321848826Z 2026 Chlamydia trachomatis conjugate vaccine CPAF pig STING agonist swine 5722717 b application/pdf http://creativecommons.org/licenses/by/4.0/