Abstract
Multiple antigenic peptide (MAP) vaccines have advantages over traditional Toxoplasma gondii vaccines, but are more susceptible to enzymatic degradation. As an effective delivery system, chitosan microspheres (CS) can overcome this obstacle and act as a natural adjuvant to promote T helper 1 (Th1) cellular immune responses. In this study, we use chitosan microparticles to deliver multiple antigenic epitopes from GRA10 (G10E), containing three dominant epitopes. When G10E was entrapped within chitosan microparticles (G10E-CS), adequate peptides for eliciting immune response were loaded in the microsphere core and this complex released G10E peptides stably. The efficiency of G10E-CS was detected both in vitro, via cell culture, and through in vivo mouse immunization. In vitro, G10E-CS activated Dendritic Cells (DC) and T lymphocytes by upregulating the secretion of costimulatory molecules (CD40 and CD86). In vivo, Th1 biased cellular and humoral immune responses were activated in mice vaccinated with G10E-CS, accompanied by significantly increased production of IFN-γ, IL-2, and IgG, and decreases in IL-4, IL-10, and IgG1. Immunization with G10E-CS conferred significant protection with prolonged survival in mice model of acute toxoplasmosis and statistically significant decreases in cyst burden in murine chronic toxoplasmosis. The results from this study indicate that chitosan microspheres used as an effective system to deliver a linked antigenic peptides is a promising strategy for the development of efficient vaccine against T. gondii.
Highlights
Toxoplasma gondii is an important medical pathogen that infects approximately 30% of the global population
The IgG test showed that all the B cell epitopes from granule protein 10 (GRA10) could recognize the IgG in the serum of BALB/c mice infected by T. gondii, in which GRA10192−215 (P1) was demonstrated to induce highest level of IgG (Figure 2Aa)
Mice immunized with P1(B cell epitope), P5(CD4+ T cell epitope), P7(CD8+ T cell epitope) or G10E were tested for B cell antibody level and T cell proliferation ability
Summary
Toxoplasma gondii is an important medical pathogen that infects approximately 30% of the global population. Toxoplasmosis is asymptomatic in immune-competent hosts, it can result in severe symptoms in immunocompromised individuals due to cerebral cyst reactivation. Another potentially fatal presentation is vertical transmission in the fetus, which can result in encephalitis, neonatal malformations, or spontaneous abortion (Blader et al, 2015; Dimier-Poisson et al, 2015). Traditional vaccine development strategies against T. gondii mainly focused on subunit and DNA vaccines Their use raises several issues, since subunit vaccines have poor stability and may cause undesired immune responses (Skwarczynski and Toth, 2014), and DNA vaccines have the theoretical risk of genomic integration into host cells (Kofler et al, 2004)
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