Genetic immunization with plasmid DNA coding for the ROP2 protein of Toxoplasma gondii

Leyva, Rosario; Hérión, Pascal; Saavedra, Rafael

doi:10.1007/s004360000296

Cited by 67 publications

(44 citation statements)

References 30 publications

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“…TSA2 was obtained from the Wiktor strain of T. gondii as described elsewhere (41). The temperature-sensitive mutant ts-4 strain of T. gondii was maintained in human skin fibroblasts at 33°C as previously described (25).…”

Section: Methodsmentioning

confidence: 99%

Mycobacterial Di-O-Acyl-Trehalose Inhibits Mitogen- and Antigen-Induced Proliferation of Murine T Cells In Vitro

Saavedra

Segura

Leyva

et al. 2001

Clin Diagn Lab Immunol

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2,3-Di-O-acyl-trehalose (DAT) is a glycolipid located on the outer layer of the Mycobacterium tuberculosis cell envelope. Due to its noncovalent linkage to the mycobacterial peptidoglycan, DAT could easily interact with host cells located in the focus of infection. The aim of the present work was to study the effects of DAT on the proliferation of murine spleen cells. DAT was purified from reference strains of M. tuberculosis, or M. fortuitum as a surrogate source of the compound, by various chromatography and solvent extraction procedures and then chemically identified. Incubation of mouse spleen cells with DAT inhibited in a dose-dependent manner concanavalin A-stimulated proliferation of the cells. Experiments, including the propidium iodide exclusion test, showed that these effects were not due to death of the cells. Tracking of cell division by labeling with 5,6-carboxyfluorescein diacetate succinimidyl ester revealed that DAT reduces the rounds of cell division. Immunofluorescence with an anti-CD3 monoclonal antibody indicated that T lymphocytes were the population affected in our model. Our experiments also suggest that the extent of the suppressive activity is strongly dependent on the structural composition of the acyl moieties in DATs. Finally, the inhibitory effect was also observed on antigen-induced proliferation of mouse spleen cells specific for Toxoplasma gondii. All of these data suggest that DAT could have a role in the T-cell hyporesponsiveness observed in chronic tuberculosis.Mycobacterium tuberculosis, the infectious agent of tuberculosis, is responsible for more deaths than any other single pathogen. It causes 2 to 3 million deaths annually and accounts for more than 30% of the deaths of human immunodeficiency virus-positive individuals (13). Factors affecting the pathogenesis of tuberculosis are complex and poorly defined; however, it is well established that the major common feature in chronic tuberculosis is the suppression of the T-cell immune response (3). For instance, while immune depression and immune activation are simultaneously present in tuberculosis, more profound defects in the cell-mediated immunity, which is largely responsible for protection, are clearly correlated with more extensive tissue damages (43).M. tuberculosis synthesizes both stimulatory and suppressive components for T cells. In general, it is accepted that hostmycobacterium interactions are mediated primarily by specialized molecules expressed on the mycobacterial cell envelope. The immunosuppressive capability of M. tuberculosis is attributed at least in part to lipoarabinomannan (LAM), a major cell wall-associated lipoglycan (21,28,29). However, the M. tuberculosis cell wall contains many other distinctive and chemically unusual components, with a predominance of lipid molecules (12). According to data obtained from M. tuberculosis and M. bovis BCG strains, lipid molecules from the cell wall of mycobacteria can migrate outside from the phagocytic vacuole (1, 5). As a consequence, glycolipids noncovalently lin...

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Section: Methodsmentioning

confidence: 99%

Mycobacterial Di-O-Acyl-Trehalose Inhibits Mitogen- and Antigen-Induced Proliferation of Murine T Cells In Vitro

Saavedra

Segura

Leyva

et al. 2001

Clin Diagn Lab Immunol

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“…Apart from SAG1, other T. gondii proteins have also been tested (12,16,28,29,33,34,39,49). Recombinant GRA4 (rGRA4) combined with cholera toxin induced partial protection in C57BL/6 immunized mice against a nonlethal challenge with the 76,000-molecular-weight T. gondii strain (33).…”

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confidence: 99%

Recombinant GRA4 or ROP2 Protein Combined with Alum or thegra4Gene Provides Partial Protection in Chronic Murine Models of Toxoplasmosis

Martin

Supanitsky

Echeverria

et al. 2004

Clin Vaccine Immunol

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The efficacy of vaccination with Toxoplasma gondii recombinant GRA4 (rGRA4) and ROP2 (rRPO2) proteins and a mix of both combined with alum were evaluated in C57BL/6 and C3H mice. In C57BL/6 mice, rGRA4 and rGRA4-rROP2 immunizations generated similar levels of immunoglobulin G1 (IgG1) and IgG2a isotypes against GRA4, whereas immunizations with rROP2 and the mix induced a predominant IgG1 production against ROP2. All groups of C3H vaccinated mice exhibited higher levels of IgG1 than IgG2a. rGRA4-stimulated splenocytes from vaccinated mice produced primarily gamma interferon while those stimulated with rROP2 produced interleukin-4. Challenge of rGRA4-or rGRA4-rROP2-vaccinated mice from both strains with ME49 cysts resulted in fewer brain cysts than the controls, whereas vaccination with rROP2 alone only conferred protection to C3H mice. Immunization with a plasmid carrying the entire open reading frame of GRA4 showed a protective level similar to that of rGRA4 combined with alum. These results suggest that GRA4 can be a good candidate for a multiantigen anti-T. gondii vaccine based on the use of alum as an adjuvant.

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“…Several trials of DNA-based vaccines against toxoplasmosis have been conducted, mainly with mice and various T. gondii antigens, such as membrane-associated surface antigen SAG1 (5,32), excreted-secreted dense-granule proteins GRA1 (33,38), GRA7 (38), and GRA4 (18), and rhoptry proteins ROP2 (29,38) and ROP1 (14). These trials have been encouraging, in that they have demonstrated the development of different levels of protection in mice.…”

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confidence: 99%

TheMIC3Gene ofToxoplasma gondiiIs a Novel Potent Vaccine Candidate against Toxoplasmosis

et al. 2003

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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.

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Genetic immunization with plasmid DNA coding for the ROP2 protein of Toxoplasma gondii

Cited by 67 publications

References 30 publications

Mycobacterial Di-O-Acyl-Trehalose Inhibits Mitogen- and Antigen-Induced Proliferation of Murine T Cells In Vitro

Mycobacterial Di-O-Acyl-Trehalose Inhibits Mitogen- and Antigen-Induced Proliferation of Murine T Cells In Vitro

Recombinant GRA4 or ROP2 Protein Combined with Alum or thegra4Gene Provides Partial Protection in Chronic Murine Models of Toxoplasmosis

TheMIC3Gene ofToxoplasma gondiiIs a Novel Potent Vaccine Candidate against Toxoplasmosis

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