Li Dan, Zhang Yizhuo, Li Shiyu, Zheng Bin
School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, China.
Engineering Research Center of Novel Vaccine of Zhejiang Province, Hangzhou Medical College, Hangzhou, China.
Front Microbiol. 2023 Mar 21;14:1145114. doi: 10.3389/fmicb.2023.1145114. eCollection 2023.
() 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 . 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 ( < 0.0001). In addition, adoptive immunization using 300 μl serum and lymphocytes (5*10) 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 and may be a potential toxoplasmosis vaccine candidate for this infection.
（）可感染几乎所有温血动物，对全球公共卫生构成重大威胁。目前，针对（）尚无有效的药物或疫苗。在本研究中，对B细胞和T细胞表位的生物信息学分析显示，与表面抗原1（SAG1）相比，TGGT1_316290（TG290）具有更优效果。通过脂质纳米颗粒（LNP）技术构建了TG290 mRNA-LNP，并将其肌肉注射到BALB/c小鼠体内，探讨其免疫原性和效果。对抗体、细胞因子（IFN-γ、IL-12、IL-4和IL-10）、淋巴细胞增殖、细胞毒性T淋巴细胞活性、树突状细胞（DC）成熟以及CD4和CD8 T淋巴细胞的分析表明，TG290 mRNA-LNP在接种疫苗的小鼠中诱导了体液免疫和细胞免疫反应。此外，T-Box 21（T-bet）、核因子κB（NF-κB）p65和干扰素调节因子8（IRF8）亚基在TG290 mRNA-LNP免疫组中过表达。与对照组小鼠的生存期（<0.0001）相比，注射TG290 mRNA-LNP的小鼠生存期显著延长（18.7±3天）。此外，使用TG290 mRNA-LNP免疫小鼠的300μl血清和淋巴细胞（5×10）进行过继免疫，可显著延长这些小鼠的生存期。本研究表明，TG290 mRNA-LNP可诱导针对（）的特异性免疫反应，可能是针对这种感染的潜在弓形虫病疫苗候选物。
