Immunological evaluation of vaccines to prevent Chlamydia trachomatis infection using the human in vitro MIMIC system

The Modular Immune In vitro Construct (MIMIC) system is an established laboratory-based methodology that reproduces in vitro the human in vivo T-cell immune response. In this study, we utilized the MIMIC system to establish a dendritic cell and CD4+ T-cell co-culture model that recapitulates T helper cell responses to Chlamydia trachomatis infection in humans. We demonstrate that C. trachomatis infection induces C. trachomatis-specific IFN-γ-producing CD4+ T-cell responses, with IFN-γ as the dominant cytokine, accompanied by significant production of TNF-α, IL-13, IL-8, and IL-6. Live C. trachomatis induces stronger IFN-γ CD4+ T-cell responses than heat-killed bacteria. A C. trachomatis outer membrane protein vaccine comprising the major outer membrane protein and polymorphic membrane proteins PmpE, PmpG, and PmpH elicited limited CD4+ T-cell responses, while an attenuated Chlamydia muridarum whole cell-based vaccine (intrOv) generated robust CD4+ T-cell responses against C. trachomatis challenge, encompassing multiple genital C. trachomatis serovars. The results suggest that intrOv vaccine should advance along the clinical development pathway as a chlamydia vaccine. MIMIC represents a valuable platform for evaluating chlamydia vaccine candidates, and it can reduce time and cost required to advance vaccine candidates to clinical trials.