Intranasal immunization with CPAF combined with ADU-S100 induces an effector CD4 T cell response and reduces bacterial burden following intravaginal infection with Chlamydia muridarum

• Published in: Vaccine 2025-01, Vol.43 (Pt 1), p.126526, Article 126526
• Main Authors: Poston, Taylor B., Girardi, Jenna, Kim, Marie, Zwarycz, Peter, Polson, A. Grace, Yount, Kacy S., Hanlan, Courtne, Jaras Salas, Ian, Lammert, Sarah Mae, Arroyo, Daisy, Bruno, Tony, Wu, Manhong, Rozzelle, James, Fairman, Jeff, Esser-Kahn, Aaron P., Darville, Toni
• Format: Article
• Language: English
• Subjects: AddaS03; Adjuvants; Adjuvants, Immunologic - administration & dosage; Adjuvants, Vaccine - administration & dosage; Administration, Intranasal; ADU-S100; Agonists; Animals; Antibodies; Antigens; Bacterial Load; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - immunology; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Cell-mediated immunity; Chlamydia; Chlamydia Infections - immunology; Chlamydia Infections - prevention & control; Chlamydia muridarum; Chlamydia muridarum - immunology; Combined vaccines; CpG1826; Cytokines; Dinucleoside Phosphates - administration & dosage; Dinucleoside Phosphates - immunology; Disease transmission; Endopeptidases - administration & dosage; Endopeptidases - immunology; Female; Females; Genital tract; Immunization; Immunization - methods; Infections; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphoid tissue; Mice; Mice, Inbred C57BL; Mucosa; Mucosal; Mucosal immunity; Nanoemulsions; Nucleotides, Cyclic; Pathogens; Peptides; Protein biosynthesis; Protein synthesis; Proteins; Quaternary Ammonium Compounds; Sexually transmitted diseases; Software; Squalene; STD; Stimulators; STING; T cell; TLR9 protein; Toll-like receptors; Vaccines; Vagina - immunology; Vagina - microbiology; γ-Interferon
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2024.126526

Chlamydia trachomatis (Ct) is the most common bacterial sexually transmitted infection globally, and a vaccine is urgently needed to stop transmission and disease. Chlamydial Protease Activity Factor (CPAF) is an immunoprevalent and immunodominant antigen for CD4 T cells and B cells, which makes it a strong vaccine candidate. Due to the tolerogenic nature of the female genital tract (FGT) and its lack of secondary lymphoid tissue, effective induction of protective cell-mediated immunity will likely require potent and safe mucosal adjuvants. To address this need, we produced CPAF in a cell-free protein synthesis platform and adjuvanted it with the TLR9-agonist CpG1826, a synthetic cyclic-di-AMP (CDA) STING (stimulator of interferon genes) agonist ADU-S100, and/or the squalene oil-in-water nanoemulsion, AddaS03. We determined that intranasal immunization with CPAF plus ADU-S100 was well tolerated in female mice, induced CD4 T cells characterized by TNFα production alone or in combination with IL-17 A or IFNγ, significantly reduced bacterial shedding, and shortened the duration of infection in mice intravaginally challenged with Chlamydia muridarum. These data demonstrate the potential for CDA as a mucosal adjuvant for vaccines against Chlamydia genital tract infection.