Abstract

Toxoplasma gondii, an intracellular zoonotic protozoan parasite, is possibly the most widespread parasite of warm-blooded animals and can cause serious public health problems and economic losses worldwide. TgCDPK2, a member of the T. gondii calcium-dependent protein kinase family, was recently identified as an essential regulator for viable cyst development in T. gondii. In the present study, we evaluated the protective immunity induced by DNA vaccination based on a recombinant eukaryotic plasmid, pVAX-TgCDPK2, against acute toxoplasmosis in mice. BALB/c mice were intramuscularly immunized with pVAX-TgCDPK2 plasmid and then challenged by infection with the highly virulent RH strain of T. gondii. The specific immune responses and protective efficacy against T. gondii were analyzed by cytokine and serum antibody measurements, lymphocyte proliferation assays, flow cytometric on lymphocytes and the survival time of mice after challenge. Our results showed that mice immunized with pVAX-TgCDPK2 could elicit special humoral and cellular responses, with higher levels of IgG antibody, and increased levels of Th1-type cytokines IFN-γ, IL-12(p70), and CD3 + CD4 + CD8 − and CD3 + CD8 + CD4 − T cells, and had a prolonged survival time (14.0 ± 2.32 days) compared to control mice. These results demonstrate that pVAX-TgCDPK2 is a potential vaccine candidate against acute toxoplasmosis.

Highlights

  • Toxoplasma gondii, an obligate intracellular apicomplexan parasite, can infect almost all warm-blooded animals, including humans [4,40]

  • The results showed that specific green fluorescence was detected in HEK 293-T cells transfected with pVAXTgCDPK2, while no green fluorescence was observed in the negative control cells (Fig. 1)

  • Since calcium-dependent protein kinase (CDPK) are absent in mammals, the CDPK family has been considered a promising target for anti-T. gondii drugs and an ideal candidate antigen for vaccines [6,41,42,43]

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Summary

Introduction

Toxoplasma gondii, an obligate intracellular apicomplexan parasite, can infect almost all warm-blooded animals, including humans [4,40]. It is estimated that one-third of the human population worldwide is chronically infected by this parasite [28]. In immune-compromized individuals, such as AIDS patients, transplant recipients and certain cancer patients, toxoplasmosis can cause severe disease sometimes with fatal outcomes [8,38]. The high prevalence of T. gondii in livestock can cause sizable economic losses in animal industries [35]. Infected animals may be a source of secondary infection since humans can be infected by consuming uncooked or undercooked meat from infected livestock [20]. Current chemotherapy against toxoplasmosis only targets the tachyzoite stage, while no effective drugs are recommended to treat the bradyzoite stage [5]. Vaccination was naturally considered as an alternative strategy to alleviate the burden of infection

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