A VCG-Based Multiepitope <i>Chlamydia</i> Vaccine Incorporating the Cholera Toxin A1 Subunit (MECA) Confers Protective Immunity Against Transcervical Challenge

Background/Objectives: We generated a novel recombinant Vibrio cholerae ghost (rVCG)-based subunit vaccine incorporating the A1 subunit of cholera toxin (CTA1) and a multiepitope Chlamydia trachomatis (CT) antigen (MECA) derived from five chlamydial outer membrane proteins (rVCG-MECA). The ability of this vaccine to protect against a CT transcervical challenge was evaluated. Methods: Female C57BL/6J mice were immunized and boosted twice two weeks apart with rVCG-MECA or rVCG-gD2 (antigen control) via the intramuscular (IM) or intranasal (IN) route. Naïve mice or mice immunized IN with live CT served as negative and positive controls, respectively. Results: Vaccine delivery stimulated robust humoral and cell-mediated immune effectors, characterized by local mucosal and systemic antigen-specific IgG, IgG2c and IgA antibody and IFN-γ (Th1 cytokine) responses. The IgG2c and IgA antibody responses elicited in both serum and vaginal secretions persisted for 112 days postimmunization. Immunization with rVCG-MECA afforded levels of protective immunity comparable to that provided by IN immunization with live CT EBs without any side effects, irrespective of route of vaccine delivery. Conclusions: These results highlight the potential of a multiepitope vaccine as a promising resource for protecting against CT genital infection and the potential of CTA1 on the VCG platform as a mucosal and systemic adjuvant for developing CT vaccines.