TheMIC3Gene ofToxoplasma gondiiIs a Novel Potent Vaccine Candidate against Toxoplasmosis

Abstract

Infection with the intracellular protozoan parasite Toxoplasma gondii causes serious public health problems and is of great economic importance worldwide. The micronemal protein MIC3, which is a potent adhesin of T. gondii, could be a significant candidate vaccine against toxoplasmosis. In this study, all CBA/J mice intramuscularly vaccinated with a plasmid encoding the immature form of the MIC3 protein (pMIC3i) produced specific anti-MIC3 immunoglobulin G (IgG) antibodies, and their sera displayed high antibody titers. This response was increased by the coadministration of a plasmid encoding the granulocyte-macrophage colony-stimulating factor (pGM-CSF). Similarly, a specific and significant cellular immune response was obtained in mice immunized with pMIC3i, and this response was markedly enhanced by pGM-CSF coadministration. The cellular immune response was associated with the production of gamma interferon IFN-␥ and interleukin-2 (IL-2), indicating that this was a Th1-type response. This was confirmed by the production of large amounts of IgG2a. Mice immunized with pMIC3i displayed significant protection against an oral challenge with T. gondii 76K cysts, exhibiting fewer brain cysts than did the control mice. Coadministration of pGM-CSF enhanced this protection. In conclusion, this study describes the design of a potent DNA vaccine encoding the novel T. gondii target antigen, MIC3 protein, that elicits a strong specific immune response as well as providing effective protection against T. gondii infection. In the attempt to achieve complete protection against toxoplasmosis, MIC3 is a good candidate vaccine which could be combined with other relevant and previously described candidates, such as SAG1 and GRA4.

Protective Immune Response in BALB/c Mice Induced by DNA Vaccine of the ROP8 gene of Toxoplasma gondii

“…4,22 The ROP8 vaccinated animals in our studies showed that antigenspecific spleen cells secreted high levels of IFN-γ. We also found that there is a significant correlation between the presence of high levels of IFN-γ secreting cells and degree of protection conferred.…”

“…It may be possible to provide complete protection against T. gondii infection by combining ROP8 with other immunogenic proteins as previously described, such as ROP16, ROP18, MIC3, SAG1, and GRA4. 4,7,22,25,26 …”

“…However, the vaccine potential of ROP8 has not been evaluated. 22 Therefore, in this study we evaluated the vaccine potential of ROP8 DNA by evaluating the vaccine-induced protective immune response against toxoplasmosis in mouse model.…”

Development of Improved Preventive and Treatment Strategies for Controlling of Toxoplasmosis in Saudi Arabia

“…The antigen-specific IgG antibodies levels in serum samples were identified pre and post-treatment as previously described (Ismael et al, 2003). The TAg of T. gondii at 10 µg mL −1 was used to coat micro titer plates.…”

Protective effect of DNA-mediated immunization with liposome-encapsulated GRA4 against infection of Toxoplasma gondii

“…Recombinant GRA4 (rGRA4) combined with cholera toxin induced partial protection for immunized C57BL/6 mice against a nonlethal challenge with the 76K T. gondii strain (Leyva et al, 2001). Administration of a plasmid encoding the granulocyte macrophage colony-stimulating factor (pGM-CSF) enhanced the protection induced by immunization with plasmid encoding the protein MIC3 (Ismael et al, 2003). Co-inoculation of plasmids expressing GRA4 (pGRA4) and SAG1 (pSAG1mut) with pGM-CSF reduced mortality of susceptible C57BL/6 mice upon oral challenge with cysts of the 76K type II strain (Mévélec et al, 2005).…”