Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA, Silver Spring, MD, USA.
Department of Parasitology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.
Nat Commun. 2023 Nov 2;14(1):7028. doi: 10.1038/s41467-023-42732-2.
The leishmanin skin test was used for almost a century to detect exposure and immunity to Leishmania, the causative agent of leishmaniasis, a major neglected tropical disease. Due to a lack of antigen used for the intradermal injection, the leishmanin skin test is no longer available. As leishmaniasis control programs are advancing and new vaccines are entering clinical trials, it is essential to re-introduce the leishmanin skin test. Here we establish a Leishmania donovani strain and describe the production, under Good Laboratory Practice conditions, of leishmanin soluble antigen used to induce the leishmanin skin test in animal models of infection and vaccination. Using a mouse model of cutaneous leishmaniasis and a hamster model of visceral leishmaniasis, soluble antigen induces a leishmanin skin test response following infection and vaccination with live attenuated Leishmania major (LmCen). Both the CD4 and CD8 T-cells are necessary for the leishmanin skin test response. This study demonstrates the feasibility of large-scale production of leishmanin antigen addressing a major bottleneck for performing the leishmanin skin test in future surveillance and vaccine clinical trials.
利什曼素皮肤试验曾用于近一个世纪，以检测利什曼原虫（导致利什曼病的病原体）的暴露和免疫情况，而利什曼病是一种主要的被忽视热带病。由于皮内注射所用抗原的缺乏，利什曼素皮肤试验已不再可用。随着利什曼病控制项目的推进和新疫苗进入临床试验，重新引入利什曼素皮肤试验至关重要。在这里，我们建立了一株杜氏利什曼原虫，并描述了在良好实验室规范条件下生产利什曼素可溶性抗原，用于在感染和接种减毒活利什曼原虫（LmCen）的动物模型中诱导利什曼素皮肤试验。使用皮肤利什曼病的小鼠模型和内脏利什曼病的仓鼠模型，可溶性抗原在感染和接种后诱导利什曼素皮肤试验反应。CD4 和 CD8 T 细胞均对利什曼素皮肤试验反应必不可少。本研究证明了大规模生产利什曼素抗原的可行性，解决了未来监测和疫苗临床试验中进行利什曼素皮肤试验的主要瓶颈。
