CTL induction by DNA vaccine with Toxoplasma gondii-HSP70 gene

Chu, Deyong; Moroda, Masataka; Li, Piao; Aosai, Fumie

doi:10.1016/j.parint.2014.01.002

Cited by 15 publications

(6 citation statements)

References 49 publications

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“…It was previously shown that when Tg HSP70 plasmids are used to vaccinate mice, CD8 + and CD4 + cytotoxic T lymphocytes are induced and mediate resistance to T. gondii infection (Chu et al, 2014). Additionally, percentage of CD4 + and CD8 + T lymphocytes was higher 1 week after immunization with 100 μg r Tg HSP70 (Zhuo et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Immunization studies with Tg HSP70 gene-encoding plasmid reduce parasite numbers in the brain and protect mice against Tg HSP70-induced anaphylactic reaction (Mohamed et al, 2003; Kikumura et al, 2010). This plasmid-based immunization is dependent on the activation of dendritic cells that lead to Th1 polarization and activation of CD8 + cytotoxic T lymphocytes that reduce parasite numbers in vitro and in vivo (Makino et al, 2011; Chu et al, 2014). On the other hand, immunization of mice with r Tg HSP70 emulsified with CFA by intraperitoneal route reduced protective immunity against T. gondii infection with RH or Fukaya strain (Mun et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Recombinant TgHSP70 Immunization Protects against Toxoplasma gondii Brain Cyst Formation by Enhancing Inducible Nitric Oxide Expression

Czarnewski

Araújo

Oliveira

et al. 2017

Front. Cell. Infect. Microbiol.

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Toxoplasma gondii is known to cause congenital infection in humans and animals and severe disease in immunocompromised individuals; consequently development of vaccines against the parasite is highly necessary. Under stress conditions, T. gondii expresses the highly immunogenic heat shock protein 70 (TgHSP70). Here, we assessed the protective efficacy of rTgHSP70 immunization combined with Alum in oral ME-49 T. gondii infection and the mechanisms involved on it. It was observed that immunized mice with rTgHSP70 or rTgHSP70 adsorbed in Alum presented a significantly reduced number of cysts in the brain that was associated with increased iNOS+ cell numbers in the organ, irrespective the use of the adjuvant. Indeed, ex vivo experiments showed that peritoneal macrophages pre-stimulated with rTgHSP70 presented increased NO production and enhanced parasite killing, and the protein was able to directly stimulate B cells toward antibody producing profile. In addition, rTgHSP70 immunization leads to high specific antibody titters systemically and a mixed IgG1/IgG2a response, with predominance of IgG1 production. Nonetheless, it was observed that the pretreatment of the parasite with rTgHSP70 immune sera was not able to control T. gondii internalization and replication by NIH fibroblast neither peritoneal murine macrophages, nor anti-rTgHSP70 antibodies were able to kill T. gondii by complement-mediated lysis, suggesting that these mechanisms are not crucial to resistance. Interestingly, when in combination with Alum, rTgHSP70 immunization was able to reduce inflammation in the brain of infected mice and in parallel anti-rTgHSP70 immune complexes in the serum. In conclusion, immunization with rTgHSP70 induces massive amounts of iNOS expression and reduced brain parasitism, suggesting that iNOS expression and consequently NO production in the brain is a protective mechanism induced by TgHSP70 immunization, therefore rTgHSP70 can be a good candidate for vaccine development against toxoplasmosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Recombinant TgHSP70 Immunization Protects against Toxoplasma gondii Brain Cyst Formation by Enhancing Inducible Nitric Oxide Expression

Czarnewski

Araújo

Oliveira

et al. 2017

Front. Cell. Infect. Microbiol.

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“…Only a few previous T. gondii vaccine studies have evaluated adoptive transfer ( 61 ). The transfer of splenocytes is more involved than the transfer of serum in T. gondii vaccine studies ( 62 , 63 ). In addition, splenocyte transfer experiments have been used in research into other parasites, such as Trypanosoma cruzi and Leishmania donovani ( 64 , 65 ).…”

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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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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“…Signalling molecules, TRIF and HMGB1, have been successfully tested as genetic adjuvants for DNA vaccines [102]. Similarly, co-transfection with HSP70 enhanced better CTL responses to DNA vaccines [103]. PD-1 based plasmids were shown to enhance DNA-vaccine-induced CD8+ T cell responses against HIV [104].…”

Section: Plasmid-encoded Signalling Moleculesmentioning

confidence: 99%

Molecular mechanisms for enhanced DNA vaccine immunogenicity

Petrovsky

2015

Expert Review of Vaccines

269

252

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Summary In the two decades since their initial discovery, DNA vaccines technologies have come a long way. Unfortunately, when applied to human subjects inadequate immunogenicity is still the biggest challenge for practical DNA vaccine use. Many different strategies have been tested in preclinical models to address this problem, including novel plasmid vectors and codon optimization to enhance antigen expression, new gene transfection systems or electroporation to increase delivery efficiency, protein or live virus vector boosting regimens to maximise immune stimulation, and formulation of DNA vaccines with traditional or molecular adjuvants. Better understanding of the mechanisms of action of DNA vaccines has also enabled better use of the intrinsic host response to DNA to improve vaccine immunogenicity. This review summarizes recent advances in DNA vaccine technologies and related intracellular events and how these might impact on future directions of DNA vaccine development.

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CTL induction by DNA vaccine with Toxoplasma gondii-HSP70 gene

Cited by 15 publications

References 49 publications

Recombinant TgHSP70 Immunization Protects against Toxoplasma gondii Brain Cyst Formation by Enhancing Inducible Nitric Oxide Expression

Recombinant TgHSP70 Immunization Protects against Toxoplasma gondii Brain Cyst Formation by Enhancing Inducible Nitric Oxide Expression

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

Molecular mechanisms for enhanced DNA vaccine immunogenicity

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