Microbiology Spectrum (Jan 2024)
A novel mRNA vaccine, TGGT1_278620 mRNA-LNP, prolongs the survival time in BALB/c mice with acute toxoplasmosis
Abstract
ABSTRACT 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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