Abstract
Chlamydia trachomatis is the most prevalent bacterial sexually transmitted infection globally. Antibiotic treatment is highly effective, but infection is often asymptomatic resulting in most individuals going undetected and untreated. This untreated infection can ascend to the upper female genital tract to cause pelvic inflammatory disease, tubal factor infertility, and ectopic pregnancy. Chlamydia screening and treatment programs have failed to control this epidemic and demonstrate the need for an efficacious vaccine to prevent transmission and disease. Animal models and human epidemiological data reveal that natural immunity can provide partial or short-lived sterilizing immunity. These data further demonstrate the importance of eliciting interferon gamma (IFNγ)-producing cluster of differentiation 4 (CD4) T cells (Th1 and Th1/17 cells) that can likely synergize with antibody-mediated opsonophagocytosis to provide optimal protection. These studies have guided preclinical rational vaccine design for decades and the first Phase 1 clinical trials have recently been completed. Recent advances have led to improvements in vaccine platforms and clinically safe adjuvants that help provide a path forward. This review describes vaccine models, correlates of immunity, antigen and adjuvant selection, and future clinical testing for Chlamydia vaccine development.