Live-attenuated PruΔgra72 strain of Toxoplasma gondii induces strong protective immunity against acute and chronic toxoplasmosis in mice

作者：Jing Li, Kang Yu, Zexuan Wu, Shufeng Yang, Yuyang Tian, Xingquan Zhu, Xiao-Nan Zheng · 发表于：Parasites & Vectors · 年份：2024 · DOI：10.1186/s13071-024-06461-9 · 被引用次数：12 · 研究领域：Toxoplasma gondii Research Studies、Legionella and Acanthamoeba research、Parasitic infections in humans and animals

Abstract Background Toxoplasma gondii is an intracellular opportunistic pathogenic protozoan that poses serious threats, particularly in immunocompromised individuals. In the absence of a robust prophylactic measure, the mitigation and management of toxoplasmosis present formidable challenges to public health. We recently found that GRA72 plays an important role in parasitophorous vacuole (PV) morphology, growth and virulence of T. gondii . However, whether gra72 -deficient strain can be used as a vaccine remains unknown. Methods We first examined the attenuated virulence of gra72 gene knockout strain (PruΔ gra72 ) and the parasite load in organs of the infected mice. Subsequently, we evaluated the immune-protective effects of the PruΔ gra72 vaccination against challenge with various types of T. gondii tachyzoites and Pru cysts. Furthermore, levels of antibodies and cytokines induced by PruΔ gra72 vaccination were examined. Statistical analysis was conducted by Student’s t-test or Mantel-Cox log-rank test based on data obtained from three independent experiments with GraphPad Prism 8.0. Results We found that PruΔ gra72 strain exhibited a significantly attenuated virulence even at the highest dose of 5 × 10 7 tachyzoites in Kunming mice model. The significant decrease of brain cyst burden and parasite load in the organs of the PruΔ gra72 -infected mice suggested its potentiality as a live-attenuated vaccine. Hence, we explored the protective immunity of PruΔ gra72 vaccination ...