Increased immune cell infiltration contribute to enhanced protective immunity following co-delivery of VCG Chlamydia vaccine with Flt3L

Abstract

Abstract Chlamydia trachomatis remains the commonest bacterial cause of sexually transmitted infections worldwide and can lead to pelvic inflammatory disease and infertility. Although antibiotics are effective against Chlamydia, most infections are asymptomatic suggesting the use of an effective vaccine may be the best approach for preventing these infections and the associated sequelae. We previously showed rectal (IR) immunization was a viable mucosal route for inducing female genital tract immunity and that the Fms-like tyrosine kinase 3-ligand (Flt3L; FL) enhanced the protective immunity of a Vibrio cholerae ghost (VCG)-based Chlamydia vaccine. However, the mechanism of immune enhancement was not investigated. In this study, we investigated if differences in the type and number of immune cells infiltrating mucosal and systemic tissues of mice could account for the observed immune enhancement following immunization. Mice were immunized IR with rVCG co-expressing the C. trachomatis polymorphic membrane protein D (PmpD) and porin B (PorB) proteins (rVCG-PmpD/PorB) with and without FL. Vaccine evaluation was based on measurement of IFN-γ cytokine, T cell proliferation, protection against intravaginal infection, and the differential profile of immune cells infiltrating mucosal and systemic tissues of mice using flow cytometry. The results showed co-delivery of vaccine with FL significantly enhanced IFN-γ levels and proliferation of splenic CD4+ immune T cells, as well as increased infiltration of immune cells in the spleen and genital tract tissues of mice. The results indicate the increased immune cell infiltration contribute to the enhanced protective immunity following co-delivery of VCG vaccine with FL.