Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China; Anhui Provincial Key Laboratory of Microbiology & Parasitology, Anhui Medical University, Hefei 230032, China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China; Anhui Provincial Key Laboratory of Microbiology & Parasitology, Anhui Medical University, Hefei 230032, China; School of Nursing, Anhui Medical University, Hefei 230601, China.
Acta Trop. 2019 Nov;199:105148. doi: 10.1016/j.actatropica.2019.105148. Epub 2019 Aug 16.
Toxoplasma gondii, a ubiquitous and obligate intracellular pathogen, belonging to the phylum Apicomplexa, is capable of infecting a broad range of warm-blooded hosts including birds and mammals that is nearly worldwide. Preventive measures for toxoplasmosis are currently lacking and as such, development of novel vaccines is of urgent need. The plant-like calcium-dependent protein kinases (CDPKs) expressed by T. gondii, play important roles in cell invasion, gliding motility, egress and some other developmental processes, in which T. gondii CDPK3 (TgCDPK3) has been implicated as an important virulence factor. In this study, the immune protective function of recombinant TgCDPK3 (rTgCDPK3) against experimental toxoplasmosis in BALB/c were evaluated. We divided the mice into different dose groups of vaccines and all immunizations with purified rTgCDPK3 protein were injected by intramuscular at weeks 0, 2, and 4 in BALB/c mice. The rTgCDPK3 vaccine provided protection was correlated with the development of humoral and cellular immune responses demonstrated through the antigen-specific spleen cell proliferation, release of Th1 cytokines IFN-γ, and the production of the high titers of IgG antibody with a predominance of IgG2a over IgG1. Vaccination with rTgCDPK3 conferred partial protection against acute toxoplasmosis, as demonstrated by prolonged survival rate after lethal challenge. Additionally, the amount of brain tissues cysts in vaccinated mice led to 46.5% reduction compared with non-vaccinated ones. These data demonstrated that rTgCDPK3 inoculation prevents or attenuates the harmful influence of T. gondii infection, and it is a potential vaccine candidate against toxoplasmosis.
刚地弓形虫,一种普遍存在且专性细胞内寄生的病原体,属于顶复门,能够感染包括鸟类和哺乳动物在内的几乎全球范围的温血宿主。目前尚无针对弓形虫病的预防措施,因此急需开发新型疫苗。弓形虫表达的植物样钙依赖性蛋白激酶(CDPKs)在细胞入侵、滑行运动、出芽和一些其他发育过程中发挥重要作用,其中弓形虫 CDPK3(TgCDPK3)被认为是一种重要的毒力因子。在这项研究中,评估了重组 TgCDPK3(rTgCDPK3)对 BALB/c 实验性弓形虫病的免疫保护作用。我们将小鼠分为不同剂量组的疫苗,所有用纯化的 rTgCDPK3 蛋白进行的免疫接种均通过肌肉内注射在 BALB/c 小鼠中进行,在第 0、2 和 4 周。rTgCDPK3 疫苗提供的保护与体液和细胞免疫反应的发展相关,通过抗原特异性脾细胞增殖、Th1 细胞因子 IFN-γ的释放以及 IgG 抗体的高滴度产生,其中 IgG2a 占优势 IgG1。rTgCDPK3 疫苗接种对急性弓形虫病具有部分保护作用,如在致命性挑战后延长生存率所示。此外,与未接种疫苗的小鼠相比,接种疫苗的小鼠脑组织中的囊数量减少了 46.5%。这些数据表明,rTgCDPK3 接种可预防或减轻弓形虫感染的有害影响,是一种潜在的弓形虫病疫苗候选物。