Resistance to Chronic<i>Toxoplasma gondii</i>Infection Induced by a DNA Vaccine Expressing GRA16

Hu, Ling-Ying; Zhang, Nian‐Zhang; Zhang, Fu-Kai; Wang, Meng; Gao, Qi; Wang, Jin‐Lei; Zhu, Xing‐Quan

doi:10.1155/2017/1295038

Cited by 12 publications

(11 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, a significantly higher level of splenocyte proliferative response was induced by DNA immunization with pDsRed2-GRA8. This result was similar to those of previous studies reporting that DNA vaccination with GRA7 and GRA16 could increase splenocyte proliferation compared with that in controls [ 25 , 26 ]. These results suggest that a cellular immune response was elicited in the immunized mice.…”

Section: Discussionsupporting

confidence: 92%

See 1 more Smart Citation

Evaluation of Protective Immune Response Induced by a DNA Vaccine Encoding GRA8 against Acute Toxoplasmosis in a Murine Model

Chu

Huang

et al. 2018

Korean J Parasitol

View full text Add to dashboard Cite

Toxoplasma gondii is an apicomplexan zoonotic protozoan parasite that infects most species of warm-blooded animals, including humans. The heavy incidence and severe or lethal damage caused by T. gondii infection clearly indicate a need for the development of an effective vaccine. T. gondii GRA8 is a member of the dense granules protein family and is used as a marker of acute infection. In the present study, we evaluated the protective immunity induced by DNA vaccination based on a recombinant eukaryotic plasmid, pDsRed2-GRA8, against acute toxoplasmosis in mice. BALB/c mice were intramuscularly immunized with the pDsRed2-GRA8 plasmid and then challenged by infection with the highly virulent GFP-RH strain of T. gondii. The specific immune responses and protective efficacy against T. gondii of this vaccine were analyzed by measuring cytokine and serum antibody titers, splenocyte proliferation assays, and the survival times of mice after challenge. Our results showed that mice immunized with pDsRed2-GRA8 demonstrated specific humoral and cellular responses, induced higher IgG antibody titers with predominant IgG2a production; increased levels of IL-10, IL-12 (p70), IFN-γ, TNF-α, and splenocyte proliferation; and prolonged survival times compared to those of control mice. The present study showed that DNA immunization with pDsRed2-GRA8 induced humoral and cellular immune responses, and all immunized mice showed greater Th1-type immune responses and longer survival times than those of control mice. These results indicated that T. gondii GRA8 DNA immunization induces a partial protective effect against acute toxoplasmosis.

show abstract

Section: Discussionsupporting

confidence: 92%

“…The vaccine candidate antigens involved in protective immunity against T. gondii include membrane-associated surface antigens (SAGs) and secreted GRAs, MICs and ROPs [ 16 – 24 ]. However, none of these antigens could completely inhibit tissue cyst formation [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Protective Immune Response Induced by a DNA Vaccine Encoding GRA8 against Acute Toxoplasmosis in a Murine Model

Chu

Huang

et al. 2018

Korean J Parasitol

View full text Add to dashboard Cite

show abstract

“…Immunization with a DNA vaccine encoding T. gondii superoxide dismutase (TgSOD) could trigger strong humoral and cellular immune responses, and had a significant increase in the survival days (median survival of 12.5 days) in comparison to the control groups against acute T. gondii ME49 strain infection in the BALB/c mice ( 52 ). Another study showed the Kunming mice immunized with pVAX-GRA16 could slightly prolong the survival time (8.4 ± 0.78 days, p > 0.05) and significantly decrease brain cysts (43.89%, p < 0.05) compared to those in all the controls ( 53 ). The survival time in BALB/c mice vaccinated with pSAG4 (9.3 ± 1.64 days) was longer than that of the mice injected by PBS or nothing after virulent T. gondii RH strain challenge.…”

Section: Discussionmentioning

confidence: 98%

GRA24-Based DNA Vaccine Prolongs Survival in Mice Challenged With a Virulent Toxoplasma gondii Strain

et al. 2019

View full text Add to dashboard Cite

Toxoplasma gondii causes infections in a wide range of intermediate hosts and remains a threatening disease worldwide because of the lack of effective drugs and vaccines. Dense granule protein 24 (GRA24) is a novel essential virulence factor that is transferred into the nucleus of host cells from the parasitophorous vacuole to regulate gene expression. In the present study, bioinformatic analysis showed that GRA24 had a high score for B-cell and T-cell epitopes compared with surface antigen 1 (SAG1), which has been studied as a promising vaccine candidate. As a DNA vaccine, pVAX1-GRA24 was injected intramuscularly into BALB/c mice and the induced immune response was evaluated. pVAX1-GRA24 induced high levels of a mixed Th1/Th2 cytokines at 6 weeks after immunization. Antibody determinations, cytokines [interferon gamma (IFN-γ), interleukin (IL)-12, IL-4, IL-10], antigen-specific lymphocyte proliferation, CD4+ and CD8+ T lymphocytes, and cytotoxic T lymphocyte activity showed that mice immunized with pVAX1-GRA24 produced specific humoral and cellular immune responses. The expression levels of interferon regulatory factor 8 (IRF8), nuclear factor kappa B (NF-κB), and T-Box 21 (T-bet) were significantly higher in the pVAX1-GRA24 immunization group than in the control groups. Survival times were prolonged significantly (24.6 ± 5.5 days) in the mice immunized with pVAX1-GRA24 compared with the mice in the control groups, which died within 7 days of T. gondii challenge (p < 0.05). The results of the present study showed that pVAX1-GRA24 induced a T. gondii-specific immune response and thus represents a promising candidate vaccine to treat toxoplasmosis.

show abstract

“…In previous studies, some DNA vaccine candidates encoding GRA protein of T. gondii , such as GRA6, GRA7, GRA2, GRA15, GRA16, GRA24, and GRA25, have demonstrated some efficacy against T. gondii infection, with their ability of eliciting immunity, particularly cellular immune responses, which is critical for defending against acute and chronic toxoplasmosis in animal models ( Chen et al, 2015 ; Hu et al, 2017 ; Xu et al, 2019 ; Zheng et al, 2019 ). In the present study, we constructed a DNA vaccine expressing TgGRA39, and evaluated its immunogenicity and protective efficacy against infection with the highly virulent T. gondii RH strain and the chronic T. gondii PRU strain.…”

Section: Discussionmentioning

confidence: 99%

Immunization With a DNA Vaccine Encoding the Toxoplasma gondii’ s GRA39 Prolongs Survival and Reduce Brain Cyst Formation in a Murine Model

Zhu

Xu²,

Lü

et al. 2021

Front. Microbiol.

View full text Add to dashboard Cite

Toxoplasma gondii, an obligate intracellular protozoan parasite, can cause infect almost all warm-blooded animals and humans. To evaluate the immunogenicity and protective efficacy of T. gondii GRA39 (TgGRA39) in mice by using DNA immunization, we constructed a recombinant eukaryotic plasmid pVAX-TgGRA39. The specific immune responses in immunized mice were analyzed by serum antibody and cytokine measurements, lymphocyte proliferation assays and flow cytometry of T lymphocyte subclasses. Also, protective efficacy against acute and chronic T. gondii infection was assessed by observing the survival time after challenge with the highly virulent T. gondii RH strain (Genotype I) and counting the number of cyst-forming in brain at 4 weeks post-infection with the cyst-forming PRU strain of T. gondii (Genotype II), respectively. Our results showed that DNA immunization with pVAX-GRA39 via intramuscular injection three times, at 2-week intervals could elicit humoral and cellular immune response, indicated by enhanced levels of IgG and IgG2a antibodies (a slightly elevated IgG2a to IgG1 ratio), and increased levels of cytokines IFN-γ, IL-2, IL-12, IL-17A, IL-17F, IL-22 and IL-23 and percentages of CD3+ CD4+ CD8- and CD3+ CD8+ CD4– T cells, in contrast to non-immunized mice. The significant increase in the expression levels of IL-6, TGF-β1, IL-1β, and the transcription factor factors RORγt, RORα, and STAT3 involved in the activation and pathway of Th17 and Tc17 cells, were also observed. However, no significant difference was detected in level of IL-4 and IL-10 (p > 0.05). These effective immune responses had mounted protective immunity against T. gondii infection, with a prolonged survival time (16.80 ± 3.50 days) and reduced cyst numbers (44.5%) in comparison to the control mice. Our data indicated that pVAX-TgGRA39 could induce effective humoral, and Th1-type, Th17, and Tc17 cellular immune responses, and may represent a promising vaccine candidate against both acute and chronic T. gondii infection.

show abstract

Resistance to ChronicToxoplasma gondiiInfection Induced by a DNA Vaccine Expressing GRA16

Cited by 12 publications

References 35 publications

Evaluation of Protective Immune Response Induced by a DNA Vaccine Encoding GRA8 against Acute Toxoplasmosis in a Murine Model

Evaluation of Protective Immune Response Induced by a DNA Vaccine Encoding GRA8 against Acute Toxoplasmosis in a Murine Model

GRA24-Based DNA Vaccine Prolongs Survival in Mice Challenged With a Virulent Toxoplasma gondii Strain

Immunization With a DNA Vaccine Encoding the Toxoplasma gondii’ s GRA39 Prolongs Survival and Reduce Brain Cyst Formation in a Murine Model

Contact Info

Product

Resources

About