Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China; The Research Center for Infectious Diseases, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China; The Provincial Key Laboratory of Zoonoses of High Institutions in Anhui, Anhui Medical University, Hefei 230032, China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China; The Research Center for Infectious Diseases, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China; The Provincial Key Laboratory of Zoonoses of High Institutions in Anhui, Anhui Medical University, Hefei 230032, China.
Vaccine. 2024 Feb 27;42(6):1342-1351. doi: 10.1016/j.vaccine.2024.01.050. Epub 2024 Feb 2.
Toxoplasma gondii (T. gondii) is one of the most common pathogenic protozoa in the world, and causes toxoplasmosis, which in varying degrees causes significant economic losses and poses a serious public health challenge globally. To date, the development of an effective vaccine for human toxoplasmosis remains a challenge. Given that T.gondii calcium-dependent protein kinase 3 (CDPK3), dense granule protein 35 (GRA35) and rhoptry organelle protein 46 (ROP46) play key roles during Toxoplasma gondii invasion of host cells, we developed a protein vaccine cocktail including these proteins and validated its protective efficacy. The specific protective effects of vaccine on mice were analyzed by measuring serum antibodies, cytokines, splenocyte proliferation, the percentage of CD and CD T-lymphocytes, survival rate, and parasite cyst burden. The results showed that mice vaccinated with a three-protein cocktail produced the highest levels of immune protein antibodies to IgG, and high levels of IFN-γ, IL-2, IL-4, and IL-10 compared to other mice vaccinated with two proteins. In addition, CD and CD T cell percentages were significantly elevated. Compared to the control groups, mice vaccinated with the three-protein cocktail survived significantly longer after acute infection with T. gondii and had significantly fewer cysts after chronic infection. These results demonstrated that a cocktail vaccine of TgCDPK3, TgGRA35, and TgROP46 can effectively induce cellular and humoral immune responses with good protective effects in mice, indicating its potential as vaccine candidates for toxoplasmosis.
刚地弓形虫（Toxoplasma gondii）是世界上最常见的致病性原生动物之一，可引起弓形体病，在不同程度上造成重大经济损失，并在全球范围内对公共卫生构成严重挑战。迄今为止，人类弓形体病的有效疫苗的开发仍然是一个挑战。鉴于刚地弓形虫钙依赖性蛋白激酶 3（CDPK3）、致密颗粒蛋白 35（GRA35）和伸头蛋白 46（ROP46）在刚地弓形虫入侵宿主细胞过程中发挥关键作用，我们开发了一种包含这些蛋白的蛋白疫苗鸡尾酒，并验证了其保护效力。通过测量血清抗体、细胞因子、脾细胞增殖、CD 和 CD T 淋巴细胞的百分比、存活率和寄生虫包囊负荷，分析了疫苗对小鼠的具体保护作用。结果表明，与接种两种蛋白的小鼠相比，接种三蛋白鸡尾酒的小鼠产生了针对 IgG 的免疫蛋白抗体的最高水平，以及高水平的 IFN-γ、IL-2、IL-4 和 IL-10。此外，CD 和 CD T 细胞的百分比显著升高。与对照组相比，急性感染刚地弓形虫后，接种三蛋白鸡尾酒的小鼠存活时间明显延长，慢性感染后囊数量明显减少。这些结果表明，TgCDPK3、TgGRA35 和 TgROP46 的鸡尾酒疫苗可有效诱导细胞和体液免疫应答，并在小鼠中具有良好的保护效果，表明其有作为弓形体病疫苗候选物的潜力。
