Abstract
Recently we reported the immune-potentiating capacity of a Chlamydia nanovaccine (PLGA-rMOMP) comprising rMOMP (recombinant major outer membrane protein) encapsulated in extended-releasing PLGA [poly (D, L-lactide-co-glycolide) (85:15)] nanoparticles. Here we hypothesized that PLGA-rMOMP would bolster immune-effector mechanisms to confer protective efficacy in mice against a Chlamydia muridarum genital challenge and re-challenge. Female BALB/c mice received three immunizations, either subcutaneously (SC) or intranasally (IN), before receiving an intravaginal challenge with C. muridarum on day 49 and a re-challenge on day 170. Both the SC and IN immunization routes protected mice against genital challenge with enhanced protection after a re-challenge, especially in the SC mice. The nanovaccine induced robust antigen-specific Th1 (IFN-γ, IL-2) and IL-17 cytokines plus CD4+ proliferating T-cells and memory (CD44high CD62Lhigh) and effector (CD44high CD62Llow) phenotypes in immunized mice. Parallel induction of antigen-specific systemic and mucosal Th1 (IgG2a, IgG2b), Th2 (IgG1), and IgA antibodies were also noted. Importantly, immunized mice produced highly functional Th1 avidity and serum antibodies that neutralized C. muridarum infectivity of McCoy fibroblasts in-vitro that correlated with their respective protection levels. The SC, rather than the IN immunization route, triggered higher cellular and humoral immune effectors that improved mice protection against genital C. muridarum. We report for the first time that the extended-releasing PLGA 85:15 encapsulated rMOMP nanovaccine confers protective immunity in mice against genital Chlamydia and advances the potential towards acquiring a nano-based Chlamydia vaccine.
Highlights
Chlamydia trachomatis is an intracellular pathogen and recognizably the most common agent of bacterial sexually transmitted diseases globally, with over 100 million new cases per year [1, 2]
We recently reported that PLGA-rMOMP induced heightened adaptive immune responses in mice immunized via the SC rather than the IN route [13]
We investigated the capacity of the PLGA-rMOMP nanovaccine to confer protective efficacy in mice against a C. muridarum genital challenge and re-challenge
Summary
Chlamydia trachomatis is an intracellular pathogen and recognizably the most common agent of bacterial sexually transmitted diseases globally, with over 100 million new cases per year [1, 2]. There is a broad consensus that developing a highly effective Chlamydia vaccine to eradicate the disease and reduce global infection cases is urgently warranted. Both attenuated or inactivated whole organisms’ vaccines supposedly can induce adequate protection against many pathogens since they contain an array of antigens [3]. One reason for the lag in developing a Chlamydia subunit vaccine, such as MOMP, is perhaps, the lack of a robust adjuvant-delivery system that can provide a prolonged targeted-delivery and bolstering of protective immune responses [6, 7]
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