Protective efficacy of two novel DNA vaccines expressing<i>Toxoplasma gondii</i>rhomboid 4 and rhomboid 5 proteins against acute and chronic toxoplasmosis in mice

Zhang, Nian‐Zhang; Xu, Ying; Wang, Meng; Petersen, Eskild; Chen, Jia; Huang, Si-Yang; Zhu, Xing‐Quan

doi:10.1586/14760584.2015.1061938

Cited by 38 publications

(36 citation statements)

References 31 publications

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“…The immunization of mice with pDsRed2-GRA8 could induce significantly higher levels of IgG antibodies than those in the controls ( P <0.05), which would contribute to strong protective efficacy against T. gondii infection. These results were in agreement with those of previous studies that vaccinated mice with plasmids encoding GRA7, GRA17, GRA23, ROM5, and ROP38 [ 10 , 26 , 37 , 38 ].…”

Section: Discussionsupporting

confidence: 93%

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

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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.

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Section: Discussionsupporting

confidence: 93%

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

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“…The results showed that the onset of symptoms were later in immunized mice, which had prolonged survival times and reduced brain cysts compared with negative controls. Zhang et al [38] constructed a pVAX-TgROM4 DNA vaccine and evaluated the immunogenicity in Kunming mice. They showed that the TgROM4 DNA vaccine induced strong humoral and cellular responses and was a potential vaccine candidate against toxoplasmosis.…”

Section: Discussionmentioning

confidence: 99%

Protection via a ROM4 DNA vaccine and peptide against Toxoplasma gondii in BALB/c mice

et al. 2017

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Background Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite with a broad host range including most warm-blooded animals, including humans. T. gondii surface antigen 1 (SAG1) is a well-characterized T. gondii antigen. T. gondii expresses five nonmitochondrial rhomboid intramembrane proteases, TgROM1-5. TgROM4 is uniformly distributed on the surface of T. gondii and involved in regulating MIC2, MIC3, MIC6, and AMA1 during T. gondii invasion of host cells. Bioinformatics have predicted ROM4 B-cell and T-cell epitopes. Immunization strategy is also a key factor in determining the effectiveness of the immune response and has gained increasing attention in T. gondii vaccine research. In this study, we used a DNA prime-peptide boost vaccination regimen to assess the protective efficacy of various vaccination strategies using TgROM4.MethodsWe identified a polypeptide (YALLGALIPYCVEYWKSIPR) using a bioinformatics approach, and immunized mice using a DNA-prime and polypeptide-boost regimen. BALB/c mice were randomly divided into six groups, including three experimental groups (peptide, pROM4 and pROM4/peptide) and three control groups (PBS, pEGFP-C1 and pSAG1). Mice were then immunized intramuscularly four times. After immunization, IgG and cytokine productions were determined using enzyme-linked immunosorbent assays. The survival time of mice was evaluated after challenge with tachyzoites of T. gondii RH strain. Additionally, the number of cysts in the brain was determined after intragastric challenge with cysts of T. gondii PRU strain.ResultsMice vaccinated with different immunization regimens (peptide, pROM4 and pROM4/peptide) elicited specific humoral and cellular responses, with high levels of IgG, IgG2a, and interferon (IFN)-γ. Moreover, IgG, IgG2a and IFN-γ levels were highest in the pROM4/peptide group. Immunized mice, especially those in the pROM4/peptide group, had prolonged survival times after challenge with tachyzoites and reduced numbers of brain cysts after infection compared with negative controls.ConclusionA DNA prime-peptide boost regimen based on ROM4 elicited the highest level of humoral and cellular immune responses among immunization regimens, and may be a promising approach to increase the efficacy of DNA immunization.

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“…Serum samples were collected after clot retraction and were stored at –80°C until analysis. The total and subclasses of anti- T. gondii IgG antibodies as an indicator of Th1 and Th2 responses were determined by ELISA as previously described (30, 31). Briefly, wells of 96-well microtiter plates were coated with 100 µl (10 µg/ml) STAg (diluted in PBS) and were incubated at 4°C overnight.…”

Section: Methodsmentioning

confidence: 99%

Immunization with Toxoplasma gondii GRA17 Deletion Mutant Induces Partial Protection and Survival in Challenged Mice

et al. 2017

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Toxoplasmosis remains a world-threatening disease largely because of the lack of a fully effective vaccine. Here, we created a ΔGRA17 mutant by disrupting the virulence factor GRA17 using CRISPR-Cas9 method. Then, we tested whether ΔGRA17 tachyzoites can be used as a live-attenuated vaccine against acute, chronic, and congenital Toxoplasma gondii infection in mice. Immune response evoked by ΔGRA17 immunization suggested a sequential Th1 and Th2 T cell response, indicated by high levels of Th1 and a mixed Th1/Th2 cytokines at 28 and 70 days after immunization, respectively. ΔGRA17-mediated immunity fully protected mice against lethal infection with wild-type (wt) RH strain, heterologous challenge with PYS, and TgC7 strains of the Chinese ToxoDB#9 genotype, and T. gondii Pru strain. Although parasite cysts were detected in 8 out of 10 immunized mice, cyst burden in the brain was significantly reduced (P < 0.05) in immunized mice (53 ± 15 cysts/brain) compared to non-immunized mice (4,296 ± 687 cysts/brain). In respect to congenital infection, the litter size, survival rate, and body weight (BW) of pups born to ΔGRA17-immunized dams were not different compared to pups born to naïve control dams (P = 0.24). However, a marked reduction in the litter size (P < 0.001), survival rate, and BW (P < 0.01) of pups born to non-immunized and infected dams was detected. Also, immunized dams infected with type II Pru strain had significantly (P < 0.001) less cyst burden in the brain compared with non-immunized and infected dams. These findings show that immunization with ΔGRA17 strain evokes cell-mediated and neutralizing antibody responses and confers some degree of protection against challenge with homologous and heterologous virulent T. gondii strains.

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Protective efficacy of two novel DNA vaccines expressingToxoplasma gondiirhomboid 4 and rhomboid 5 proteins against acute and chronic toxoplasmosis in mice

Abstract: The pVAX-TgROM5 showed a better protective efficacy against acute and chronic toxoplasmosis compared to pVAX-TgROM4.

Cited by 38 publications

References 31 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

Protection via a ROM4 DNA vaccine and peptide against Toxoplasma gondii in BALB/c mice

Immunization with Toxoplasma gondii GRA17 Deletion Mutant Induces Partial Protection and Survival in Challenged Mice

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