Evaluating Potential Vaccine Antigens in both the Chlamydia trachomatis and Chlamydia muridarum Intravaginal Mouse Challenge Models

Abstract

Identifying relevant animal challenge models adds to the complexity of human vaccine development. Murine challenge models have been the most utilized animal model for Chlamydia trachomatis vaccine development. The question arises as to whether the C. trachomatis or C. muridarum pre-clinical model is optimal. We compared C. muridarum and C. trachomatis intravaginal challenge models in a combined total of seventy-five studies evaluating potential vaccine candidates. In 100% (42/42) of C. muridarum studies, mice immunized with Chlamydia elementary bodies (EB) demonstrated a significant reduction in urogenital bacterial shedding as measured by qPCR (p < 0.05) compared to adjuvant-control-immunized mice. Significant reduction in urogenital shedding was observed for EB-immunized groups in only 82% (27/33) of C. trachomatis studies. We have evaluated proposed vaccine antigens in both models and observed immunization with Chlamydia major outer membrane protein (MOMP) vaccine formulations to be protective (p < 0.05) in both models, immunization with polymorphic membrane protein serovar D (PmpD) p73 passenger domain was protective only in the C. trachomatis model, and immunization with PmpD p82 translocator domain was not protective in either model. We also observed in both models that depletion of CD4+ T-cells in MOMP-immunized mice resulted in diminished protective immunity but animals were still able to reduce the infection level. In contrast, mice immunized with live EBs by intraperitoneal route did not require CD4+ T-cells to resolve urogenital infection from intravaginal challenge in either model. Overall, we have found the C. muridarum model to be a more robust, reliable, and reproducible model for vaccine antigen discovery.