Abstract Chlamydia trachomatis infections are the most common bacterial STIs globally and can lead to serious morbidity if untreated. Development of a killed, whole-cell vaccine has been stymied by coincident epitope destruction during inactivation. Here, we present a prototype Chlamydia vaccine composed of elementary bodies (EBs) from the related mouse pathogen, Chlamydia muridarum (Cm). EBs inactivated by gamma rays (Ir-Cm) in the presence of the antioxidant Mn2+-Decapeptide (DEHGTAVMLK) Phosphate (MDP) are protected from epitope damage but not DNA damage. Cm EBs gamma-inactivated with MDP retain their structure and provide significant protection in a murine genital tract infection model. Mice vaccinated with Ir-Cm (+MDP) exhibited elevated levels of Cm-specific IgG and IgA antibodies, reduced bacterial burdens, accelerated clearance, and distinctive cytokine responses compared to unvaccinated controls and animals vaccinated with EBs irradiated without MDP. Preserving EB epitopes with MDP during gamma inactivation offers the potential for a polyvalent, whole-cell vaccine against C. trachomatis.
