Immunization with Live-Attenuated RHΔhad2a Strain Confers Partial Protective Immunity against Acute and Chronic Infection of Toxoplasma gondii in Mice

文献类型： 外文期刊

第一作者： Zhang, Hai-Sheng

作者： Zhang, Hai-Sheng;Cao, Hui;Li, Chen-Xu;Zhu, Xing-Quan;Zheng, Xiao-Nan;Zhang, Hai-Sheng;Zhang, Zhi-Wei;Wang, Meng

作者机构： Shanxi Agr Univ, Coll Vet Med, Lab Parasit Dis, Jinzhong 030801, Peoples R China;Chinese Acad Agr Sci, Lanzhou Vet Res Inst, State Key Lab Anim Dis Control & Prevent, Key Lab Vet Parasitol Gansu Prov, Lanzhou 730046, Peoples R China

关键词： Toxoplasma gondii; toxoplasmosis; HAD phosphatase; CRISPR-Cas9; live-attenuated strain; vaccine

期刊名称：PATHOGENS （ 2022影响因子：3.7； 五年影响因子：3.7 ）

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年卷期： 2024 年 13 卷 2 期

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收录情况： SCI

摘要： Toxoplasmosis caused by Toxoplasma gondii is an important zoonosis of human and animal health significance. Current chemical therapeutics have side effects, and no commercially available vaccine is licensed for the prevention of toxoplasmosis in humans and most animals. Developing a safe and effective vaccine with long-term protection against T. gondii infection is necessary to control toxoplasmosis. HAD2a is a key member of the haloacid dehalogenase (HAD) phosphatase family, which is essential for T. gondii daughter budding. However, the role of HAD2a in T. gondii virulence remains unknown. In this study, we successfully constructed the had2a gene knockout strain in the T. gondii-type I RH strain (RH Delta had2a) and determined its role in virulence and vaccination. These results demonstrate that HAD2a played an important role in parasite daughter budding and in vitro replication. Knockout of the had2a gene attenuated the virulence of the T. gondii-type I RH strain. Vaccination with RH Delta had2a tachyzoites induced a Th1-biased immune response, provided partial protection against acute T. gondii infection in mice by highly virulent tachyzoites of RH and PYS (ToxoDB#9, Chinese I) strains, and conferred strong protection against challenge infection by cysts and oocysts of the less virulent type II Pru strain. These results demonstrate that T. gondii had2a is important for its in vitro proliferation and virulence in mice and that RH Delta had2a may be used as a candidate strain to generate a multiple gene knockout live-attenuated strain or be collaboratively applied with other live-attenuated strains to confer more effective protection against T. gondii infection.

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