PLGA-encapsulated Chlamydia recombinant MOMP enhances serum and mucosal Th1 antibodies including memory and effector T-cells via subcutaneous prime-boost as compared to the intramuscular priming route immunization of mice

Abstract

Abstract Vaccine developmental efforts are rapidly targeting biodegradable nanoparticles-based vaccines with encapsulated antigen. We have developed a PLGA 85/15 (poly (lactic-co-glycolic acid) Chlamydia nanovaccine by encapsulating its recombinant MOMP (major outer membrane protein) that induced robust adaptive immune responses and provided enhanced protection against C. muridarum (Cm) challenge in subcutaneously immunized mice. In the current study, we compared the immunogenicity and efficacy of priming routes; subcutaneous (sc) or intramuscular (im) followed by two sc-boosts to evaluate serum and mucosal antibodies [Th1 (IgG2a, IgG2b), Th2 (IgG1)] as well as memory and effector T-cells activation after immunization and Cm challenge of mice. We observed significantly high levels of MOMP-specific serum and mucosal antibodies with high avidity especially for Th1 antibodies. A significant increase in Th1 serum and mucosal antibodies with even higher avidity was observed after genital tract Cm challenge in the sc-prime-boost immunized mice. Evaluation of the Th1/Th2 antibody titer ratio revealed that the nanovaccine evoked a higher Th1 and lower Th2 response, which skewed to a dominated Th1 antibody response after bacterial exposure to sc-prime mice. In addition, CD4+ memory (CD44highCD62Lhigh) and effector (CD44highCD62Llow) T-cells proliferation was about two-fold higher in the sc-prime mice. Herein, we reveal that the subcutaneous prime-boost immunization with the nanovaccine was more effective in enhancing the Th1 antibody response and memory and effector T-cell responses against a chlamydial genital tract challenge of mice.