Synergistic effect of rSAG1 and rGRA2 antigens formulated in PLGA microspheres in eliciting immune protection against Toxoplasama gondii

Abstract

There is still no human vaccine against Toxoplasma gondii (T. gondii), as one of the most successful parasites. In present study, we designed a subunit vaccine composed of recombinant SAG1 (rSAG1) and recombinant GRA2 (rGRA2) proteins. In order to improve the induced immune responses, rSAG1 and rGRA2 were adsorbed on Poly (DL-lactide-co-glycolide) (PLGA) microspheres (MS) prepared by double emulsion solvent evaporation method. BALB/c mice were subcutaneously vaccinated by rSAG1-adsorbed PLGA MS (rSAG1-PLGA), rGRA2-adsorbed PLGA MS (rGRA2-PLGA), and the mixture of both formulations (rSAG1/rGRA2-PLGA), twice with a 3-week interval. PLGA MS characteristics, protein release, cellular and humoral immune responses, and protection against acute toxoplasmosis were evaluated. All vaccinated mice induced significantly partial protection and longer survival times associated with higher IFN-γ/IL-10 ratio and higher amount of Toxoplasma-specific IgG antibodies compared to control groups. Interestingly, the synergistic effect of rSAG1 and rGRA2 in eliciting more potent cellular and humoral responses and consequently higher protection in comparison to single antigen was confirmed.This study introduces the mixture of rSAG1 and rGRA2 (derived from different stages of Toxoplasma life-cycle) formulated in PLGA MS as a promising candidate in vaccine development against T. gondii.