Evaluation of immuno-efficacy of a novel DNA vaccine encoding Toxoplasma gondii rhoptry protein 38 (TgROP38) against chronic toxoplasmosis in a murine model

Abstract

Background

Toxoplasma gondii is an obligate intracellular parasite which can infect almost all mammalian animals, leading to toxoplasmosis. T. gondii rhoptry protein 38 (TgROP38) is an active rhoptry protein kinase which is involved in the inhibitory effect on host cell transcription by down-regulating the MAPK signaling track.

Methods

TgROP38 gene was amplified and inserted into eukaryotic vector pVAX I and formed the DNA vaccine pVAX-ROP38. Mice in the experimental group were intramuscularly immunized with pVAX-ROP38 and those injected with pVAX I, PBS or nothing were treated as controls. After three injections at two week intervals, all mouse groups were challenged intraperitoneally with 1000 tachyzoites of the virulent T. gondii RH strain (Type I, ToxoDB #10) and 10 cysts of the PRU strain (Type II, ToxoDB #1), respectively.

Results

Mice inoculated with pVAX-ROP38 vaccine had a higher level of IgG antibodies ( P < 0.01) and T lymphoproliferative response. The high ratio of IgG2a/IgG1 and the increasing levels of IFN-γ and IL-2 ( P < 0.05) indicated an activated Th1 cell-mediated immune responses. Furthermore, the CD4 ⁺ and CD8 ⁺ proportions in vaccinated mice were also increased significantly compared with that in mice of the three control groups ( P < 0.01). In the model of acute infection, the average survival time of mice in the pVAX-ROP38 group (8.1 days ± 0.75) was no statistically different compared to that in the PBS, pVAX I and blank control groups which died within 7 days. However, in the model of chronic infection, the brain cyst reduction in the pVAX-ROP38 group reached 76.6%, compared to controls ( P < 0.01).

Conclusions

The present study revealed that the pVAX-ROP38 vaccine could elicit strong humoral and cell immunity response against chronic T. gondii infection in mice, resulting in the reduction of the brain cyst formation effectively, which suggests that TgROP38 is a desirable vaccine candidate against chronic T. gondii infection.