Protective Efficacy of a Toxoplasma gondii Rhoptry Protein 13 Plasmid DNA Vaccine in Mice

Wang, Peiyuan; Yuan, Zihao; Petersen, Eskild; Li, Jie; Zhang, Xiu‐Xiang; Li, Xiuzhen; Li, Haoxin; Lv, Z.; Cheng, Tian; Ren, Di; Yang, Genhua; Lin, Rui-Qing; Zhu, Xing‐Quan

doi:10.1128/cvi.00397-12

Cited by 40 publications

(33 citation statements)

References 26 publications

(23 reference statements)

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“…Rhoptry proteins (ROPs) were shown to exist on the parasitophorous vacuole membrane and were also identified to be the virulence factors participating in T. gondii invasion [ 14 , 15 ]. Due to their key biological roles, T. gondii rhoptry proteins 5, 13, 16 and 18 (TgROP5, TgROP13, TgROP16 and TgROP18) have been proven as potential vaccine candidates [ 16 – 19 ]. T. gondii rhoptry protein 38 (TgROP38) is predicted to be an active rhoptry protein kinase (ROPK) that could have an inhibitory effect on host cell transcription by down-regulating the MAPK signaling track [ 20 – 22 ].…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Tan

et al. 2014

BMC Infect Dis

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BackgroundToxoplasma 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.MethodsTgROP38 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.ResultsMice 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).ConclusionsThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-525) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

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

Zhang

Tan

et al. 2014

BMC Infect Dis

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“…An effective human vaccine against T. gondii infection is currently unavailable. DNA, subunit or protein vaccines against T. gondii have been studied but were unsuccessful [3,4]. As such, finding novel vaccines that are highly effective against T. gondii in-fection remains a great challenge for researchers.…”

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Virus-like Particle Vaccine Containing Toxoplasma gondii Rhoptry Protein 13 Induces Protection against T. gondii ME49 Infection in Mice

et al. 2019

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Toxoplasma gondii can infect humans worldwide, causing serious diseases in pregnant women and immunocompromised individuals. T. gondii rhoptry protein 13 (ROP13) is known as one of the key proteins involved in host cell invasion. In this study, we generated virus-like particles (VLPs) vaccine expressing T. gondii rhoptry ROP13 and investigated VLPs vaccine efficacy in mice. Mice immunized with ROP13 VLPs vaccine elicited significantly higher levels of T. gondii-specific IgG, IgG1, IgG2a, and IgA antibody responses following boost immunization and challenge infection, whereas antibody inductions were insignificant upon prime immunization. Differing immunization routes resulted in differing antibody induction, as intranasal immunization (IN) induced greater antibody responses than intramuscular immunization (IM) after boost and challenge infection. IN immunization induced significantly higher levels of IgG and IgA antibody responses from feces, antibody-secreting cells (ASCs), CD4 + T, CD8 + T cells and germinal center B cell responses in the spleen compared to IM immunization. Compared to IM immunization, IN immunization resulted in significantly reduced cyst counts in the brain as well as lesser body weight loss, which contributed to better protection. All of the mice immunized through either route survived, whereas all naïve control mice perished. These results indicate that the ROP13 VLPs vaccine could be a potential vaccine candidate against T. gondii infection.

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“…In recent years, DNA vaccination has been demonstrated to elicit a predominantly Th1 immune response: inducing CD4 ϩ T-lymphocyte and CD8 ϩ cytotoxic T-lymphocyte (CTL) responses against the administered antigen (14, 16) and several T. gondii DNA vaccine candidates evaluated using this administration route (17,18,19,20,21,22) have shown effective protection against T. gondii infection. Also, DNA vaccines are promising tools in the development of safe and effective vaccines against T. gondii infection in both humans and animals (14), and thus it would be valuable to identify novel T. gondii antigens for use in DNA vaccination.…”

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Evaluation of Immune Responses in Mice after DNA Immunization with Putative Toxoplasma gondii Calcium-Dependent Protein Kinase 5

Zhang

Huang

et al. 2014

Clin. Vaccine Immunol.

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dToxoplasma gondii can cause serious public health problems and economic losses worldwide. Calcium-dependent protein kinases (CDPKs) are key mediators of T. gondii signaling pathways and are implicated as important virulence factors. In the present study, we cloned a novel T. gondii CDPK gene, named TgCDPK5, and constructed the eukaryotic expression vector pVAX-CDPK5. Then, we evaluated the immune protection induced by pVAX-CDPK5 in Kunming mice. After injection of pVAX-CDPK5 intramuscularly, immune responses, determined with lymphoproliferative assays and cytokine and antibody measurements, were monitored, and mouse survival times and brain cyst formation were evaluated following challenges with the T. gondii RH strain (genotype I) and the PRU strain (genotype II). pVAX-CDPK5 effectively induced immune responses with increased specific antibodies, a predominance of IgG2a production, and a strong lymphocyte proliferative response. The levels of gamma interferon (IFN-␥), interleukin 2 (IL-2), and IL-12(p70) and the percentages of CD3 ؉ CD4 ؉ and CD3 ؉ CD8 ؉ cells in mice vaccinated with pVAX-CDPK5 were significantly increased. However, IL-4 and IL-10 were not produced in the vaccinated mice. These results demonstrate that pVAX-CDPK5 can elicit strong humoral and cellular Th1 immune responses. The survival time of immunized mice challenged with the T. gondii RH strain (8.67 ؎ 4.34 days) was slightly, but not significantly, longer than that in the control groups within 7 days (P > 0.05). The numbers of brain cysts in the mice in the pVAX-CDPK5 group were reduced by ϳ40% compared with those in the control groups (P < 0.05), which provides a foundation for the further development of effective subunit vaccines against T. gondii.

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Protective Efficacy of a Toxoplasma gondii Rhoptry Protein 13 Plasmid DNA Vaccine in Mice

Cited by 40 publications

References 26 publications

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

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

Virus-like Particle Vaccine Containing Toxoplasma gondii Rhoptry Protein 13 Induces Protection against T. gondii ME49 Infection in Mice

Evaluation of Immune Responses in Mice after DNA Immunization with Putative Toxoplasma gondii Calcium-Dependent Protein Kinase 5

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