Regulation of CD8+ T cell responses to infection with parasitic protozoa

Jordan, Kimberly A.; Hunter, Christopher A.

doi:10.1016/j.exppara.2010.05.008

Cited by 67 publications

(61 citation statements)

References 170 publications

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“…Due to the obligate intracellular lifestyle, T cell-mediated adaptive immune responses involving in CD4+ and CD8+ T cells are known to be important in resistance against primary T. gondii infection and reactivation of chronic toxoplasmosis [26-28]. In the present study, a significantly proliferative response of splenocytes from pVAX-CDPK3 vaccinated mice indicated that vigorous cellular immune responses were induced by the DNA vaccine.…”

Section: Discussionsupporting

confidence: 50%

Protective immunity against Toxoplasma gondiiinduced by DNA immunization with the gene encoding a novel vaccine candidate: calcium-dependent protein kinase 3

et al. 2013

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BackgroundToxoplasma gondii can infect almost all warm-blood animals including human beings. The plant-like calcium-dependent protein kinases (CDPKs) harbored by T. gondii are involved in gliding motility, cell invasion, egress and some other developmental processes, and so have been implicated as important virulence factors.MethodsIn the present study, we constructed a DNA vaccine expressing T. gondii CDPK3 (TgCDPK3) and evaluated its protective efficacy against T. gondii infection in Kunming mice. The gene sequence encoding TgCDPK3 was inserted into the eukaryotic expression vector pVAX I, and mice were immunized with pVAX-CDPK3 intramuscularly.ResultsThe results showed that mice immunized with pVAX-CDPK3 developed a high level of specific antibodies and a strong lymphoproliferative response. The significantly increased levels of IFN-γ, IL-2, IL-12 (p70) and IL-23 and high ratio of IgG2a to IgG1 antibody titers indicated that a Th1 type response was elicited after immunization with pVAX-CDPK3. Furthermore, the percentage of CD4+ T cells in mice vaccinated with pVAX-CDPK3 was significantly increased. After lethal challenge with the tachyzoites of the virulent T. gondii RH strain, the mice immunized with pVAX-CDPK3 prolonged the survival time from 10 days to 24 days (13.5 ± 4.89) compared to untreated mice or those received PBS or pVAX I which died within 7 days (P < 0.05). In chronic infection model (10 cysts of the T. gondii PRU strain), the numbers of brain cysts of the mice immunized with pVAX-CDPK3 reduced significantly when compared with those in control groups (P < 0.05), and the rate of reduction could reach to about 50%.ConclusionsTgCDPK3 can generate protective immunity against acute and chronic T. gondii infection in Kunming mice and is a promising vaccine candidate for further development of an effective vaccine against T. gondii.

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Section: Discussionsupporting

confidence: 50%

Protective immunity against Toxoplasma gondiiinduced by DNA immunization with the gene encoding a novel vaccine candidate: calcium-dependent protein kinase 3

et al. 2013

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“…T-cell-mediated adaptive immune responses are well known to determine the course of T. gondii infection (34,35,36). In the present study, a significant proliferative response of splenocytes was induced following DNA immunization with pVAX-CDPK5, indicating an activated cellular immune response.…”

Section: Discussionmentioning

confidence: 99%

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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“…Thus, our findings are in agreement with previous reports that Th1-mediated responses are highly protective in T. gondii infection. 14,23,24 This study showed that a DNA vaccine encoding the T. gondii ROP8 protein is a simple and potent vaccine that elicits specific immune responses, and provides significant protection against a virulent strain of T. gondii. Therefore, ROP8 can be considered as a potential vaccine candidate against toxoplasmosis.…”

Section: Discussionmentioning

confidence: 99%

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

Parthasarathy¹,

Fong²,

Kalyanasundaram

et al. 2013

The American Society of Tropical Medicine and Hygiene

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Abstract. Toxoplasmosis in humans and other animals is caused by the protozoan parasite Toxoplasma gondii. During the process of host cell invasion and parasitophorous vacuole formation by the tachyzoites, the parasite secretes Rhoptry protein 8 (ROP8), an apical secretory organelle. Thus, ROP8 is an important protein for the pathogenesis of T. gondii. The ROP8 DNA was constructed into a pVAX-1 vaccine vector and used for immunizing BALB/c mice. Immunized mice developed immune response characterized by significant antibody responses, antigen-specific proliferation of spleen cells, and production of high levels of IFN-γ (816 ± 26.3 pg/mL). Challenge experiments showed significant levels of increase in the survival period (29 days compared with 9 days in control) in ROP8 DNA vaccinated mice after a lethal challenge with T. gondii. Results presented in this study suggest that ROP8 DNA is a promising and potential vaccine candidate against toxoplasmosis.

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Regulation of CD8+ T cell responses to infection with parasitic protozoa

Cited by 67 publications

References 170 publications

Protective immunity against Toxoplasma gondiiinduced by DNA immunization with the gene encoding a novel vaccine candidate: calcium-dependent protein kinase 3

Protective immunity against Toxoplasma gondiiinduced by DNA immunization with the gene encoding a novel vaccine candidate: calcium-dependent protein kinase 3

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

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

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