Chlamydia muridarumrecombinant MOMP nanovaccine induces cross-reactive antibodies against Chlamydia trachomatishuman serovars

Abstract

Abstract Chlamydia trachomatis (CT), caused by various serovars, remains the leading sexually transmitted bacterial infection worldwide. An efficient delivery system is critical to developing whole or subunit vaccines against CT, and some vaccine developmental efforts are targeting biodegradable nanoparticles-based vaccines with encapsulated antigens. We developed a nanovaccine employing the recombinant major outer membrane protein (rMOMP) of C. muridarum (Cm) encapsulated in poly(lactic acid-co-glycolic acid) 85/15 (PLGA-rMOMP). We previously compared the humoral responses of two priming routes, subcutaneous (SC) or intramuscular (IM-p), followed by two SC-boosts to evaluate rMOMP-specific serum antibodies [IgG2a, IgG2b and IgG1] produced by PLGA-rMOMP immunization of female BALB/c mice. Here we used an elementary body (EB)-specific ELISA to investigate the ability of systemic antibodies produced in immunized mice to recognize Cm and to cross-recognize human CT-serovars D, F and J. Serum from mice inoculated with PBS encapsulated PLGA served as negative control. We observed high recognition of Cm specific total IgG (8-fold) and isotypes IgG2a (8-fold), IgG2b (32-fold), IgG1 (8-fold) by SC in comparison to IM-p immunizations. We also observed IgG antibodies recognizing CT-serovars D, F and J from mice immunized via both routes. Evaluation of the Th1 (IgG2a, IgG2b)/Th2 (IgG1) antibody titer ratios revealed that immunization via the SC route induced predominantly Th1 antibodies recognizing both Cm and human CT-serovars. Our data show that mice immunized with PLGA-rMOMP produced high levels of systemic antibodies recognizing Cm, but more importantly, there was a robust serological cross-recognition of the human CT-serovars. This research was supported by the National Institute Of Allergy And Infectious Diseases of the National Institutes of Health under Award Number NIH-R21AI111159, NIH-NIGMS-RISE (1R25GM106995-01) and the National Science Foundation (NSF)-CREST (HRD-1241701) and NSF-HBCU-RISE (HRD-1646729) grants.