Chlamydia trachomatis is the most common bacterial sexually transmitted infection worldwide and is responsible for a wide range of reproductive morbidities. Vaccines are the most promising prospect for reducing the incidence of infection and pathology. Chlamydial vaccinology poses unique problems with over 70 years of vaccine research only yielding a single Phase 1 clinical trial. Here, we use an innovative vaccine development pipeline, based on reverse-vaccinology methodologies, to define novel chlamydial antigens in combination with established adjuvant technologies to accelerate translation into human clinical trials. To this end, we have identified immunodominant and immunoprevalent antigens in humans that are associated with protection against infection or reproductive pathology. Here, we define the safety, immunogenicity, and protective efficacy of these novel antigens in our established mouse model of chlamydial infection.