Physio-structural and immunological characterization of a PLGA 85/15 encapsulated Chlamydia recombinant MOMP nanovaccine candidate

R. Sahu, S. Dixit, S.R. Singh, V.A. Dennis
Alabama State University,
United States

Keywords: Chlamydia trachomatis, bacteria, MOMP (major Outer Membrane Protein), PLGA [poly (D, L-lactic-co-glycolic acid)

Summary:

The quest for vaccine development against Chlamydia trachomatis (CT), the leading cause of bacterial sexually transmitted diseases worldwide, has escalated to reduce its occurrence and global economic burden. Recently, nanovaccines have emerged as attractive candidates due to flexibility in their formulation, biodegradability, biocompatibility and adjuvant properties. Nanovaccines applicability depends on their physical properties for their immunogenicity, which is vital for biosafety and therapeutic efficacy studies. We have developed a nanovaccine against CT employing its recombinant MOMP (major outer membrane protein) by encapsulating it within PLGA [poly (D, L-lactic-co-glycolic acid) 85/15 nanoparticles. Physio-structural characterizations included Zeta sizing, Zeta potential, DSC (Differential Scanning Calorimetry), UV spectroscopy and in vitro release of rMOMP. Encapsulated rMOMP nanoparticles were small (~200 nm), thermally stable (90ÂșC) and negatively charged (-13 mV). UV spectroscopy showed minimal presence of rMOMP on the outer surface of encapsulated nanoparticles, indicating its successful encapsulation. Moreover, rMOMP was slowly released from within PLGA nanoparticles over a 31-day period, suggesting its attractiveness as a vaccine candidate. Encapsulated rMOMP was devoid of endotoxin contamination as assessed by the Polymyxin B inhibition assay using mouse J774 macrophages. Of significance was the observation that encapsulated rMOMP activated mouse dendritic cells (DCs), the major antigen presenting cells, for induction of Th1 immune responses, which are critical for protection against CT. Exposure of mouse DCs to encapsulated rMOMP at different concentrations revealed marked increase in the production of the Th1 cytokines, IL-6 and IL-12p40. Our data warrants efficacy studies in mouse for assessing the overall potential of our nanovaccine as a candidate against CT.