Wu Minmin, Liu Shutong, Chen Ying, Liu Deng, An Ran, Cai Haijian, Wang Jie, Zhou Nan, Obed Cudjoe, Han Meng, Shen Jilong, Chen Lijian, Du Jian
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
The Research Center for Infectious Diseases, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
NPJ Vaccines. 2022 Aug 20;7(1):98. doi: 10.1038/s41541-022-00518-5.
Toxoplasmosis, a common parasitic disease, is caused by Toxoplasma gondii, which infects approximately 30% of the world's population. This obligate intracellular protozoan causes significant economic losses and poses serious public health challenges worldwide. However, the development of an effective toxoplasmosis vaccine in humans remains a challenge to date. In this study, we observed that the knockout of calcium-dependent protein kinase 3 (CDPK3) in the type II ME49 strain greatly attenuated virulence in mice and significantly reduced cyst formation. Hence, we evaluated the protective immunity of ME49Δcdpk3 as a live attenuated vaccine against toxoplasmosis. Our results showed that ME49Δcdpk3 vaccination triggered a strong immune response marked by significantly elevated proinflammatory cytokine levels, such as IFN-γ, IL-12, and TNF-α, and increased the percentage of CD4 and CD8 T-lymphocytes. The high level of Toxoplasma-specific IgG was maintained, with mixed IgG1/IgG2a levels. Mice vaccinated with ME49Δcdpk3 were efficiently protected against the tachyzoites of a variety of wild-type strains, including type I RH, type II ME49, Chinese 1 WH3 and Chinese 1 WH6, as well as the cysts of wild-type strains ME49 and WH6. These data demonstrated that ME49Δcdpk3 inoculation induced effective cellular and humoral immune responses against acute and chronic Toxoplasma infections with various strains and was a potential candidate to develop a vaccine against toxoplasmosis.
弓形虫病是一种常见的寄生虫病，由刚地弓形虫引起，全球约30%的人口受到感染。这种专性细胞内原生动物在全球范围内造成了重大经济损失，并带来了严峻的公共卫生挑战。然而，迄今为止，开发一种有效的人类弓形虫病疫苗仍然是一项挑战。在本研究中，我们观察到II型ME49株中钙依赖性蛋白激酶3（CDPK3）的敲除极大地减弱了其在小鼠中的毒力，并显著减少了包囊形成。因此，我们评估了ME49Δcdpk3作为减毒活疫苗对弓形虫病的保护性免疫。我们的结果表明，接种ME49Δcdpk3引发了强烈的免疫反应，其特征是促炎细胞因子水平显著升高，如IFN-γ、IL-12和TNF-α，并增加了CD4和CD8 T淋巴细胞的百分比。弓形虫特异性IgG水平维持在较高水平，IgG1/IgG2a水平混合。接种ME49Δcdpk3的小鼠能有效抵御多种野生型菌株的速殖子，包括I型RH、II型ME49、中国1型WH3和中国1型WH6，以及野生型菌株ME49和WH6的包囊。这些数据表明，接种ME49Δcdpk3可诱导针对不同菌株急性和慢性弓形虫感染的有效细胞免疫和体液免疫反应，是开发弓形虫病疫苗的潜在候选物。
