Protective effect of a DNA vaccine cocktail encoding ROP13 and GRA14 with Alum nano-adjuvant against Toxoplasma gondii infection in mice

Pagheh, Abdol Sattar; Daryani, Ahmad; Alizadeh, Paria; Hassannia, Hadi; Oliveira, Sonia M. Rodrigues; Kazemi, Tohid; Rezaei, Fatemeh; Pereira, Maria de Lourdes; Ahmadpour, Ehsan

doi:10.1016/j.biocel.2021.105920

Cited by 8 publications

(4 citation statements)

References 46 publications

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“…Survival time is a direct and reliable indicator of the safety and efficacy of T. gondii candidate vaccines. Although the TG_620 mRNA-LNP vaccine did not induce complete protection against high virulence T. gondii infection, it did induce better partial protection than other T. gondii vaccines, such that the survival time of the mice in this study was longer than that in some previous studies ( 43 , 59 ) and even longer than that of the combined DNA vaccine ( 60 ). Mice immunized with TG_620 mRNA-LNP were able to elicit both humoral and cellular immune responses against T. gondii .…”

Section: Discussioncontrasting

confidence: 73%

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: Discussioncontrasting

confidence: 73%

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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“…The use of a genetic adjuvant successfully enhanced the protection level. As mice immunized with the ROP13-GRA14-alum nano-adjuvant exhibited significant production of IL-4 and IgG1, the Th2 immune response was developed by immunization with a DNA vaccine coated with alum nano-adjuvant ( Pagheh et al., 2021 ). Mouse priming with GRA1 DNA vaccine-loaded chitosan particles resulted in high anti-GRA1 antibodies and a higher IgG2a/IgG1 ratio ( Bivas-Benita et al., 2003 ).…”

Section: Discussionmentioning

confidence: 99%

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

Sun

Huang

et al. 2021

Front. Cell. Infect. Microbiol.

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Toxoplasma gondii infects almost all warm-blooded animals, including humans. DNA vaccines are an effective strategy against T. gondii infection, but these vaccines have often been poorly immunogenic due to the poor distribution of plasmids or degradation by lysosomes. It is necessary to evaluate the antigen delivery system for optimal vaccination strategy. Nanoparticles (NPs) have been shown to modulate and enhance the cellular humoral immune response. Here, we studied the immunological properties of calcium phosphate nanoparticles (CaPNs) as nanoadjuvants to enhance the protective effect of T. gondii dense granule protein (GRA7). BALB/c mice were injected three times and then challenged with T. gondii RH strain tachyzoites. Mice vaccinated with GRA7-pEGFP-C2+nano-adjuvant (CaPNs) showed a strong cellular immune response, as monitored by elevated levels of anti-T. gondii-specific immunoglobulin G (IgG), a higher IgG2a-to-IgG1 ratio, elevated interleukin (IL)-12 and interferon (IFN)-γ production, and low IL-4 levels. We found that a significantly higher level of splenocyte proliferation was induced by GRA7-pEGFP-C2+nano-adjuvant (CaPNs) immunization, and a significantly prolonged survival time and decreased parasite burden were observed in vaccine-immunized mice. These data indicated that CaPN-based immunization with T. gondii GRA7 is a promising approach to improve vaccination.

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“…A DNA vaccine encompassing SAG1 and ROP2 adjuvanted with the hepatitis B virus (HBV) antigen evoked an immune response contributing to the survival of immunized mice, while the unadjuvanted control groups perished by 9 days post-infection (dpi) [ 29 ]. Interestingly, unadjuvanted vaccines expressing ROP13 and GRA14 conferred better protection against T. gondii infection in the absence of adjuvants [ 30 ]. While alum-adjuvanted ROP13+GRA14 vaccines contributed to higher Th2 response induction in mice, a marginally extended survival rate was observed from mice immunized with unadjuvanted ROP13+GRA14 vaccines [ 30 ].…”

Section: Vaccine Platforms Against T Gondiimentioning

confidence: 99%

“…Interestingly, unadjuvanted vaccines expressing ROP13 and GRA14 conferred better protection against T. gondii infection in the absence of adjuvants [ 30 ]. While alum-adjuvanted ROP13+GRA14 vaccines contributed to higher Th2 response induction in mice, a marginally extended survival rate was observed from mice immunized with unadjuvanted ROP13+GRA14 vaccines [ 30 ].…”

Section: Vaccine Platforms Against T Gondiimentioning

confidence: 99%

Advances in Toxoplasma gondii Vaccines: Current Strategies and Challenges for Vaccine Development

Chu

Quan

2021

Vaccines

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Toxoplasmosis, caused by the apicomplexan parasite Toxoplasma gondii, is one of the most damaging parasite-borne zoonotic diseases of global importance. While approximately one-third of the entire world’s population is estimated to be infected with T. gondii, an effective vaccine for human use remains unavailable. Global efforts in pursuit of developing a T. gondii vaccine have been ongoing for decades, and novel innovative approaches have been introduced to aid this process. A wide array of vaccination strategies have been conducted to date including, but not limited to, nucleic acids, protein subunits, attenuated vaccines, and nanoparticles, which have been assessed in rodents with promising results. Yet, translation of these in vivo results into clinical studies remains a major obstacle that needs to be overcome. In this review, we will aim to summarize the current advances in T. gondii vaccine strategies and address the challenges hindering vaccine development.

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Protective effect of a DNA vaccine cocktail encoding ROP13 and GRA14 with Alum nano-adjuvant against Toxoplasma gondii infection in mice

Cited by 8 publications

References 46 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

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

Advances in Toxoplasma gondii Vaccines: Current Strategies and Challenges for Vaccine Development

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