Chlamydia trachomatis (CT) is the most common sexually transmitted bacterial 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. However, 70 years of CT vaccine research has yielded only one Phase 1 clinical trial. Here, we utilised a human-informed data driven vaccine design pipeline to develop an effective chlamydial vaccine. The primary correlate of protection against CT are T helper cells secreting interferon-γ. We identified novel immunoprevalent CT T cell antigens by screening immune cells from CT seropositive women for the secretion of interferon-γ by ELISPOT after antigen stimulation. Human-informed immunoprevalent antigens for further vaccine development were refined by screening ex vivo responses of Chlamydia muridarum (Cmu) infected mice which identified CPAF as the immunodominant antigen. In mice, CPAF-specific CD4+ T cells are recruited to the female genital tract (FGT) during Cmu infection and secrete interferon-γ. Intranasal immunization with recombinant CPAF combined with select adjuvants elicited robust CPAF-specific Th1 responses. Upon challenge, immunized mice had significantly lower infectious burden and earlier clearance of infection compared to mock immunized controls. To our knowledge, this is the greatest reduction of infectious burden conferred by a recombinant subunit vaccine in this model. In summary, we have identified chlamydial antigens that are immunogenic in women which are also protective when used in a subunit vaccine in the mouse model of Chlamydia infection. Designing a vaccine informed by human immune responses offers the best chance for success in future clinical trials.