Chitosan Microsphere Used as an Effective System to Deliver a Linked Antigenic Peptides Vaccine Protect Mice Against Acute and Chronic Toxoplasmosis

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.

Immunization with plasmid DNA expressing Heat Shock Protein 40 confers prophylactic protection against chronicToxoplasma gondiiinfection in Kunming mice

“…This result was higher than that obtained by DNA vaccine expressing T. gondii CDPK3 [ 40 ] and 39.08% by DNA plasmid (pVAX1-PF) encoding TgPF gene [ 13 ]. However, our result was comparable to the 57.8% reduction achieved by vaccination using multiple antigenic peptides encapsulated by chitosan microspheres [ 16 ].…”

Immunization With a DNA Vaccine Cocktail Encoding TgPF, TgROP16, TgROP18, TgMIC6, and TgCDPK3 Genes Protects Mice Against Chronic Toxoplasmosis

“…In this study, cocktail DNA vaccine achieved an 80.22% reduction in the parasite cyst burden, compared with 50% obtained by DNA vaccine expressing T. gondii CDPK3 ( 34 ) and 39.08% by DNA vaccine (pVAX1-PF) encoding TgPF gene ( 35 ). Reduction in the brain cysts’ load achieved in our study, was also greater than the 57.8% reduction achieved by vaccination using multiple antigenic peptides encapsulated by chitosan microspheres ( 36 ).…”

“…Significantly higher expression of the transcription factor T-bet ( p = 0.0010) was observed in mice in G1, compared with mice from the control group. This finding indicates that increased IFN-γ production may have resulted from T-bet-mediated activation of CD4 + T cells and natural killer (NK) cells ( 36 ). In marked contrast with IFN-γ, the level of IL-4 was not statistically different between any mouse groups.…”

Immunogenicity of a Virus-Like-Particle Vaccine Containing Multiple Antigenic Epitopes of Toxoplasma gondii Against Acute and Chronic Toxoplasmosis in Mice

“…These results are consistent with the above findings that only the mice immunized with HBc ΔH82 successfully triggered both strong humoral and cellular immune responses in all the vaccinated mice, and these two immune responses were interrelated and acted synergistically to increase protection against acute and chronic infection with T. gondii (49). Increased production of the cytokines IL-10 and IL-4, apart from IFN-γ and IL-2, may also be helpful against acute toxoplasmosis in immunized mice, because they can reduce short-term fatality by decreasing excessive and lethal Th1-type responses at the early acute stage of the disease (32, 55). A possible explanation is the activation of CD4 + T cells induced by AS15.…”

“…The percentages of the CD4 + and CD8 + T lymphocytes subsets of immunized mice were analyzed by flow cytometry as previously described (32). Briefly, 2 weeks after the last immunization, splenocyte suspensions were prepared from three immunized mice per group by pushing the spleens through a wire mesh.…”