A novel Toxoplasma gondii TGGT1_316290 mRNA-LNP vaccine elicits protective immune response against toxoplasmosis in mice

Abstract

Toxoplasma gondii (T. gondii) can infect almost all warm-blooded animals and is a major threat to global public health. Currently, there is no effective drug or vaccine for T. gondii. In this study, bioinformatics analysis on B and T cell epitopes revealed that TGGT1_316290 (TG290) had superior effects compared with the surface antigen 1 (SAG1). TG290 mRNA-LNP was constructed through the Lipid Nanoparticle (LNP) technology and intramuscularly injected into the BALB/c mice, and its immunogenicity and efficacy were explored. Analysis of antibodies, cytokines (IFN-γ, IL-12, IL-4, and IL-10), lymphocytes proliferation, cytotoxic T lymphocyte activity, dendritic cell (DC) maturation, as well as CD4+ and CD8+ T lymphocytes revealed that TG290 mRNA-LNP induced humoral and cellular immune responses in vaccinated mice. Furthermore, T-Box 21 (T-bet), nuclear factor kappa B (NF-kB) p65, and interferon regulatory factor 8 (IRF8) subunit were over-expressed in the TG290 mRNA-LNP-immunized group. The survival time of mice injected with TG290 mRNA-LNP was significantly longer (18.7 ± 3 days) compared with the survival of mice of the control groups (p < 0.0001). In addition, adoptive immunization using 300 μl serum and lymphocytes (5*107) of mice immunized with TG290 mRNA-LNP significantly prolonged the survival time of these mice. This study demonstrates that TG290 mRNA-LNP induces specific immune response against T. gondii and may be a potential toxoplasmosis vaccine candidate for this infection.

Lipid Nanoparticle (LNP) Delivery Vector-Assisted Targeted Controlled Release mRNA Vaccines in Tumor Immunity

“…Some studies have shown that LNP vectors can effectively deliver mRNA vaccines and stimulate tumor antigen-specific immune responses in tumor mouse models [161][162][163][164] . For example, some mRNA vaccines targeting tumor-specific antigens delivered through LNP carriers can induce high levels of specific antibodies and cellular immune responses, inhibit tumor growth and prolong the survival time of mice [165] .…”

Protective immunity induced by a native Toxoplasma gondii antigen against Toxoplasma infection in Balb/c mice

“…The most straightforward measure of a potential vaccine's efficacy is the percentage of vaccinated mice that can still be alive due to the T. gondii challenge. To test the mice's ability to survive, we administered intraperitoneal injections of tachyzoites from the extremely dangerous T. gondii RH strain(32). In our study, within 12 days of the RH tachyzoite test, every mouse in group IV perished.…”