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), rGRA2adsorbed 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.

The Impact of the Antigenic Composition of Chimeric Proteins on Their Immunoprotective Activity against Chronic Toxoplasmosis in Mice

“…However, these examples illustrate that multi-antigenic composition has a much greater chance of generating efficient immune responses to protect from T. gondii invasion. Furthermore, recombinant proteins administered concurrently can exhibit synergistic effects in eliciting protective immune responses [26].…”

The Immunogenic and Immunoprotective Activities of Recombinant Chimeric T. gondii Proteins Containing AMA1 Antigen Fragments

“…Although the elucidated protection was high, it was not complete; thus, the next step was to further boost the antigen's immunoprotective capacity by incorporating another antigen into the chimeric structure. The experimental design was based on the observation that recombinant proteins used concomitantly often demonstrate a synergistic effect that triggers a protective response in vaccinated animals [46]. Furthermore, the AMA1 antigen, assigned to the microneme proteins, is considered to play a critical role in host cell invasion.…”

Immune Protective Evaluation Elicited by DNA Vaccination With Neospora caninum Dense Granules Proteins in Mice

“…After invasion into host cells, N. caninum could secrete large amounts of GRA proteins, which are closely associated with its survival and intracellular replication (27). Many GRAs involved in the formation of parasitophorous vacuole and intravacuolar network structures, maintaining intracellular growing environment for tachyzoites.…”