Sepahpour Telly, Alshaweesh Jalal, Azodi Nazli, Singh Komudi, Ireland Derek D C, Valanezhad Farzaneh, Nakamura Risa, Satoskar Abhay R, Dey Ranadhir, Hamano Shinjiro, Nakhasi Hira L, Gannavaram Sreenivas
Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD, 20993, USA.
Department of Parasitology, Institute of Tropical Medicine (NEKKEN), The Joint Usage/Research Center on Tropical Disease, Nagasaki University, Nagasaki, Japan, and Graduate School of Biomedical Sciences, Doctoral Leadership Program, Nagasaki University, Nagasaki, Japan.
NPJ Vaccines. 2024 Dec 19;9(1):250. doi: 10.1038/s41541-024-01032-6.
Leishmaniasis is a tropical disease caused by Leishmania parasites and currently has no licensed vaccines. We developed a dermotropic Leishmania major centrin gene-deleted strain (LmCen) as a live attenuated vaccine. Recent studies have shown that type I interferons (IFNs) play important roles in immunity to parasitic and viral pathogens. However, their relevance in protective immunity following vaccination is not understood. We found that immunization with LmCen induces a transient increase in type I IFN response along with its regulatory factor IRF7 that is downregulated 7-21 days post-immunization, coincided with the induction of a robust Th1 adaptive immune response. Challenge infection with virulent L. donovani parasites showed a significant reduction of splenic and hepatic parasite burden in IRF7 mice than wild type mice following immunization with LmCen, suggesting that ablation of type I IFN response is a pre-requisite for the induction of LmCen mediated Th1 immunity against L. donovani infection.
利什曼病是一种由利什曼原虫寄生虫引起的热带疾病，目前尚无获批的疫苗。我们开发了一种嗜皮性杜氏利什曼原虫中心蛋白基因缺失株（LmCen）作为减毒活疫苗。最近的研究表明，I型干扰素（IFN）在针对寄生虫和病毒病原体的免疫中发挥重要作用。然而，它们在疫苗接种后保护性免疫中的相关性尚不清楚。我们发现，用LmCen免疫会诱导I型干扰素反应及其调节因子IRF7短暂增加，免疫后7-21天IRF7会下调，这与强大的Th1适应性免疫反应的诱导同时发生。在用LmCen免疫后，用强毒杜氏利什曼原虫寄生虫进行攻击感染显示，IRF7基因敲除小鼠的脾脏和肝脏寄生虫负荷比野生型小鼠显著降低，这表明消除I型干扰素反应是诱导LmCen介导的针对杜氏利什曼原虫感染的Th1免疫的先决条件。
