Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis.
Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis.
复制标题
弓形虫减毒活 ME49αcdpk3 菌株可预防急性和慢性弓形虫病
DOI：
10.1038/s41541-022-00518-5
复制
发表时间：
2022-08-20
期刊：
影响因子：
9.2
通讯作者：
中科院分区：
文献类型：
--
作者：
弓形虫病是一种常见的寄生虫病，由弓形虫引起，感染了世界上大约30%的人口。这种专性细胞内原生动物造成重大经济损失，并在世界范围内构成严重的公共卫生挑战。然而，迄今为止，在人类中开发有效的弓形虫病疫苗仍然是一个挑战。在这项研究中，我们观察到II型ME 49菌株中钙依赖性蛋白激酶3（CDPK 3）的敲除大大减弱了小鼠的毒力，并显着减少了囊肿形成。因此，我们评估了ME 49 Δ cdpk 3作为弓形虫病减毒活疫苗的保护性免疫。我们的研究结果表明，ME 49 Δ cdpk 3疫苗接种引发了强烈的免疫应答，其特征在于显著升高的促炎细胞因子水平，如IFN-γ、IL-12和TNF-α，并增加了CD 4+和CD 8 + T淋巴细胞的百分比。弓形虫特异性IgG保持高水平，IgG 1/IgG 2a水平混合。ME 49 Δ cdpk 3疫苗接种的小鼠有效地保护免受各种野生型菌株的速殖子，包括I型RH、II型ME 49、中国1 WH 3和中国1 WH 6，以及野生型菌株ME 49和WH 6的包囊。结果表明，ME 49 Δ cdpk 3能诱导小鼠产生有效的细胞免疫和体液免疫应答，有望成为弓形虫病疫苗的候选疫苗。
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.
登录
查看更多内容
弓形虫病发育中的药物：进步，挑战和当前状态。
DOI：
10.2147/dddt.s60973
发表时间：
2017
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Alday PH;Doggett JS
通讯作者：
Doggett JS
影响因子：
8
作者：
López-Yglesias AH;Burger E;Araujo A;Martin AT;Yarovinsky F
通讯作者：
Yarovinsky F
影响因子：
6.4
作者：
Ajzenberg, D;Cogné, N;Dardé, ML
通讯作者：
Dardé, ML
影响因子：
14.2
作者：
Hill, D;Dubey, JP
通讯作者：
Dubey, JP
影响因子：
2.4
作者：
BUXTON, D;INNES, EA
通讯作者：
INNES, EA