Enhancing Immune Responses to a DNA Vaccine Encoding Toxoplasma gondii GRA7 Using Calcium Phosphate Nanoparticles as an Adjuvant

Sun, Hongchao; Huang, Jing; Fu, Yuan; Hao, Lili; Liu, Xin; Shi, Tuanyuan

doi:10.3389/fcimb.2021.787635

Cited by 8 publications

(9 citation statements)

References 62 publications

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“…The TG_620 mRNA-LNP has a suppressive effect on immune pathology. Some previous T. gondii vaccines provide only Th1 immune responses without inducing Th2 immunity ( 39 – 41 ). The cytokine detection results were consistent with the antibody subtype detection results, indicating that TG_620 mRNA-LNP can induce both Th1 and Th2 immune responses in mice, with a predominance of the Th1 immune response.…”

Section: Discussionmentioning

confidence: 99%

“…CTL experiments can be conducted in vivo or in vitro ( 42 ). However, most studies about T. gondii vaccines did not involve CTL evaluations; only a few evaluated it in vitro ( 40 , 41 , 43 , 44 ). Specific activation of T lymphocytes might play an important role in developing spleen lymphocytes in TG_620 mRNA-LNP-immunized mice and induce a T. gondii -specific cellular immune response.…”

Section: Discussionmentioning

confidence: 99%

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A novel mRNA vaccine, TGGT1_278620 mRNA-LNP, prolongs the survival time in BALB/c mice with acute toxoplasmosis

Zhang,

Li,

Chu

et al. 2024

Microbiol Spectr

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Toxoplasmosis is a global health issue; however, there is a lack of safe and effective drugs and vaccines. Herein, we developed a novel mRNA vaccine, TGGT1_278620 mRNA-lipid nanoparticle (LNP), and evaluated its safety and efficacy in BALB/c mice. The vaccine elicited a significant increase not only immunoglobulin (Ig)G and IgG subclasses (IgG2a and IgG1) antibodies but also interleukin (IL)-12, interferon-gamma, IL-4, and IL-10 cytokines. We showed that specific cellular immunity and humoral immunity were activated by combining splenocyte proliferation, cytotoxic T-cell activity, and T-cell surface molecule CD8 and CD4 ratios. Dendritic cell signaling pathway members interferon regulatory factor 8, T-Box 21, and nuclear factor kappa B were analyzed at the mRNA and protein levels, and increased differentiation and maturation were observed by examining dendritic cell surface molecules (CD83, CD86, MHC-I, and MHC-II) using flow cytometry. Finally, the survival time of the vaccinated mice was significantly prolonged after Toxoplasma gondii RH challenge, and the adoptive transfer of splenocytes and sera from the vaccinated mice also significantly prolonged survival. These findings suggested that the TGGT1_278620 mRNA-LNP vaccine might be a promising candidate for further development in anti-toxoplasmosis therapy. IMPORTANCE Toxoplasma gondii , an obligate intracellular eukaryotic parasite, can infect about one-third of the world’s population. One vaccine, Toxovax, has been developed and licensed commercially; however, it is only used in the sheep industry to reduce the losses caused by congenital toxoplasmosis. Various other vaccine approaches have been explored, including excretory secretion antigen vaccines, subunit vaccines, epitope vaccines, and DNA vaccines. However, current research has not yet developed a safe and effective vaccine for T. gondii . Here, we generated an mRNA vaccine candidate against T. gondii . We investigated the efficacy of vaccination with a novel identified candidate, TGGT1_278620, in a mouse infection model. We screened T. gondii -derived protective antigens at the genome-wide level, combined them with mRNA-lipid nanoparticle vaccine technology against T. gondii , and investigated immune-related factors and mechanisms. Our findings might contribute to developing vaccines for immunizing humans and animals against T. gondii .

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A novel mRNA vaccine, TGGT1_278620 mRNA-LNP, prolongs the survival time in BALB/c mice with acute toxoplasmosis

Zhang,

Li,

Chu

et al. 2024

Microbiol Spectr

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“…Adjuvanting DNA vaccines had a minor effect on the vaccine's protective efficacy. Although supplementing the T. gondii GRA7 DNA vaccine with the calcium phosphate nanoparticle adjuvant prolonged the survival of immunized mice, it was only 2 days longer than the unadjuvanted control group [22]. Conflicting results were observed from multi-antigenic vac-Parasites Hosts Dis 2023;61(3):231-239 • https//doi.org/10.3347/PHD.22097 cines.…”

Section: Current Progress In T Gondii Dna Vaccine Developmentmentioning

confidence: 99%

Recent progress in vaccine development targeting pre-clinical human toxoplasmosis

Chu,

Quan

2023

Parasites Hosts Dis

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Toxoplasma gondii is an intracellular parasitic organism affecting all warm-blooded vertebrates. Due to the unavailability of commercialized human T. gondii vaccine, many studies have been reported investigating the protective efficacy of pre-clinical T. gondii vaccines expressing diverse antigens. Careful antigen selection and implementing multifarious immunization strategies could enhance protection against toxoplasmosis in animal models. Although none of the available vaccines could remove the tissue-dwelling parasites from the host organism, findings from these pre-clinical toxoplasmosis vaccine studies highlighted their developmental potential and provided insights into rational vaccine design. We herein explored the progress of T. gondii vaccine development using DNA, protein subunit, and virus-like particle vaccine platforms. Specifically, we summarized the findings from the pre-clinical toxoplasmosis vaccine studies involving T. gondii challenge infection in mice published in the past 5 years.

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“…Hence, rhoptry organelle proteins (ROPs) are considered promising vaccine candidates against apicomplexan diseases ( 10 ). Indeed, several T. gondii ROPs, including Tg ROP1, 5, 7, and 17, have been reported to effectively stimulate protective immunity and to significantly reduce brain cyst loads in immunized animals ( 11 – 14 ). Several E. tenella ROPs, including Et rop5405, Et rop5905 (EtROP35), Et rop27705 (EtROP30), and Et rop5190 ( Et ROP17) have been also reported to effectively stimulate protective immunity and reduce oocyst output in immunized chickens ( 15 – 18 ).…”

Section: Introductionmentioning

confidence: 99%

A rhoptry protein, localizing in the bulb region of rhoptries, could induce protective immunity against Eimeria tenella infection

Shi,

Zhou,

Kong

et al. 2023

Front. Immunol.

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BackgroundRhoptry organelle proteins (ROPs) secreted by apicomplexan parasites play important roles during parasites invasion and survival in host cells, and are potential vaccine candidates against apicomplexan diseases. Eimeria tenella (E. tenella) is one of the most noteworthy apicomplexan species, which causes hemorrhagic pathologies. Although dozens of putative E. tenella ROP sequences are annotated, most ROP proteins are not well studied.MethodsIn this study, an E. tenella ROP21 gene was identified and the recombinant EtROP21 protein (rEtROP21) was expressed in Escherichia coli. The developmental expression levels, localization, and protective efficacy against E. tenella infection in chickens were studied.ResultsAn EtROP21 gene fragment with an open reading frame (ORF) of 981 bp was obtained from the Beijing strain of E. tenella. The rEtROP21 has a molecular weight of approximately 50 kDa and was recognized by rEtROP21-immunized mouse serum. Two specific protein bands, about 43 KDa and 95 KDa in size, were detected in the whole sporozoite proteins using the rEtROP21-immunized chicken serum. RT-qPCR analysis of the E. tenella ROP21 gene (EtROP21) revealed that its mRNA levels were higher in merozoites and sporozoites than in sporulated and unsporulated oocysts. Immunofluorescence and immunoelectron analyses showed that the EtROP21 protein predominantly localizes in the bulb region of rhoptries distributed at anterior, posterior, and perinuclear regions of E. tenella sporozoites. Immunization and challenge experiments revealed that immunizing chickens with rEtROP21 significantly increased their average body weight gain while decreasing mean lesion score and oocyst output (P <0.05). When compared with the challenged control group, the rEtROP21-immunized group was associated with a significantly higher relative weight gain (90.2%) and a greater reduction in oocyst output (67%) (P <0.05). The anticoccidial index of the rEtROP21-immunized group was 163.2. Chicken serum ELISA revealed that the levels of the specific anti- rEtROP21 antibody, IFN-γ, and IL-4 were significantly higher in the rEtROP21-immunized group than in the challenged control group (P <0.05).ConclusionThese results indicate that rEtROP21 can induce a high level of specific immune response and it is a potential candidate for the development of vaccines against E. tenella infection in chickens.

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Enhancing Immune Responses to a DNA Vaccine Encoding Toxoplasma gondii GRA7 Using Calcium Phosphate Nanoparticles as an Adjuvant

Cited by 8 publications

References 62 publications

A novel mRNA vaccine, TGGT1_278620 mRNA-LNP, prolongs the survival time in BALB/c mice with acute toxoplasmosis

A novel mRNA vaccine, TGGT1_278620 mRNA-LNP, prolongs the survival time in BALB/c mice with acute toxoplasmosis

Recent progress in vaccine development targeting pre-clinical human toxoplasmosis

A rhoptry protein, localizing in the bulb region of rhoptries, could induce protective immunity against Eimeria tenella infection

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