Department of Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Acta Trop. 2021 Apr;216:105836. doi: 10.1016/j.actatropica.2021.105836. Epub 2021 Jan 21.
The causative agent of toxoplasmosis, Toxoplasma gondii (T. gondii), is able to influence the health of humans and other vertebrates. Toxoplasma may cause severe illness in the fetus and immunocompromised individuals. The high incidence and intense damages of Toxoplasma infection clearly shows the need to achieve the safe and suitable vaccine. In this study, an immunoinformatics approach was employed to design a multi-epitope DNA vaccine encoding the T. gondii SAG1, SAG3 and SAG5. The bioinformatic outputs supported the immunogenic and non-allergic natures of multi-epitope vaccine. Thereafter, the protective efficacy of the vaccine was evaluated with/without CpG-ODN adjuvant in a laboratory animal model. BALB/c mice were immunized subcutaneously with multi-epitope DNA vaccine. The in vivo findings indicated that the multi-epitope DNA vaccine elicited significant production of IgG antibodies (472.90 ± 2.74 ng/ml) as well as IFN-γ (173.71 ± 26.39 pg/ml) (p < 0.001). Moreover, a significant reduced parasite-burden (17,470 per mg of spleen) and prolonged survival time (9 days) were observed in the immunized groups compared to the controls (p < 0.05). The low values of IL-4 (22.5 ± 0.16 pg/ml) were detected in vaccinated mice compared to the control (PBS) (p > 0.05). In addition, CpG-ODN as an adjuvant increased the immune efficacy of the multi-epitope DNA vaccine. In multi-epitope vaccine+CpG-ODN group, the values of IgG antibodies (535.90 ±7.29 ng/ml) and IFN-γ (358.21 ± 32.70 pg/ml) were significanly higher than the multi-epitope vaccine group. Meanwhile, an increased survival time (10 days) and fewer parasite load (15,485 per mg of spleen) were observed in multi-epitope vaccine+CpG-ODN group. The results revealed that the DNA vaccine containing epitopes of SAG1, SAG3 and SAG5 adjuvanted with CpG-ODN might be a new model for further investigations against acute T. gondii infection.
刚地弓形虫（Toxoplasma gondii）是弓形体病的病原体，它能够影响人类和其他脊椎动物的健康。刚地弓形虫可能会导致胎儿和免疫功能低下者罹患重病。刚地弓形虫感染的高发病率和强烈损害显然表明需要开发安全合适的疫苗。在这项研究中，我们采用免疫信息学方法设计了一种编码刚地弓形虫 SAG1、SAG3 和 SAG5 的多表位 DNA 疫苗。生物信息学结果支持了多表位疫苗的免疫原性和非变应原性。此后，我们在实验室动物模型中评估了该疫苗在有/无 CpG-ODN 佐剂时的保护效力。BALB/c 小鼠经皮下免疫接种多表位 DNA 疫苗。体内研究结果表明，多表位 DNA 疫苗可显著诱导 IgG 抗体（472.90 ± 2.74 ng/ml）和 IFN-γ（173.71 ± 26.39 pg/ml）的产生（p < 0.001）。此外，与对照组（PBS）相比，免疫组的寄生虫负荷（脾脏每毫克 17,470 个）和存活时间（9 天）明显降低（p < 0.05）。与对照组（PBS）相比，接种疫苗的小鼠中 IL-4 的水平（22.5 ± 0.16 pg/ml）较低（p > 0.05）。此外，CpG-ODN 作为佐剂增加了多表位 DNA 疫苗的免疫效果。在多表位疫苗+CpG-ODN 组中，IgG 抗体（535.90 ±7.29 ng/ml）和 IFN-γ（358.21 ± 32.70 pg/ml）的水平明显高于多表位疫苗组。同时，在多表位疫苗+CpG-ODN 组中观察到存活时间延长（10 天）和寄生虫负荷减少（脾脏每毫克 15,485 个）。结果表明，含有 SAG1、SAG3 和 SAG5 表位的 DNA 疫苗与 CpG-ODN 佐剂联合使用可能是进一步研究急性刚地弓形虫感染的新模式。
