A novel vaccine against Leishmania

描述(申请人提供)：利什曼原虫是一种典型的原生动物，由血吸虫沙蝇传播，引起利什曼病。利什曼病影响着88个国家的1200万人，估计有3.5亿人面临被不同利什曼原虫种类感染的风险。每年的新病例发病率约为200万。与许多其他热带疾病一样，利什曼病与经济发展和人为环境变化有关，这增加了对沙蝇媒介的接触。这种疾病对美国来说已经变得重要起来，因为许多在伊拉克和阿富汗服役的士兵都暴露在沙蝇面前，并患有利什曼病。利什曼病/艾滋病毒混合感染正在成为一种极其严重的新疾病，而且其频率正在增加。治疗主要是基于五价锑化合物，尽管一种新药米替福辛在治疗利什曼病方面表现出了希望。不幸的是，锑化合物是有毒的，在不同的流行地区，耐药性很常见。米替福辛最近才在印度获得批准，其在现场的有效性和耐药性的发展尚不清楚。然而，抗生素，包括抗菌药物、抗真菌药物和抗病毒药物的经验表明，对当前使用的药物产生抗药性是规则，而不是例外；这就需要继续寻找新药。特别有用和缺乏的治疗手段是通过有效和安全的泛利什曼原虫疫苗进行预防。我们的长期目标是确定和开发用于预防或治疗一些人类传染病的疫苗，包括利什曼原虫引起的传染病。在这个SBIR第一阶段，我们将测试几种假定的抗原，以一种新的方式输送，在预防主要乳杆菌感染方面的效果。我们将通过两个具体的目标来实现这一点：目标一：利用重组DNA技术使酵母细胞表达四种候选蛋白质。目的二：测试每种疫苗制剂的体内效力，以保护接种的动物免受大乳杆菌的攻击。 这项工作将是第二阶段进一步工作的前奏，第二阶段的工作将包括在几个利什曼原虫感染模型中测试每个成功的候选疫苗的体内效力，以及详细了解每个配方的免疫反应。我们相信，这项工作将导致针对利什曼原虫的预防性和治疗性疫苗的开发

DESCRIPTION (provided by applicant): Leishmania are typanosomatid protozoans that are transmitted by phlebotomine sand flies causing leishmaniasis. Leishmaniasis affects 12 million people in 88 countries with an estimated 350 million people that are at risk of infection by the different species of Leishmania. The annual incidence of new cases is about 2 million. Like many other tropical diseases, the leishmaniases are related to economic development and man-made environmental changes, which increase exposure to the sandfly vector. The disease has assumed importance for the United States as many soldiers serving in Iraq and Afghanistan veterans are exposed to sand flies and are afflicted with leishmaniasis. Leishmania/HIV coinfection is emerging as an extremely serious, new disease and it is increasing in frequency. Treatment is based primarily on pentavalent antimony compounds although a new drug, miltefosine, shows promise in treating leishmaniasis. Unfortunately, the antimony compounds are toxic and resistance in various endemic regions is common. Miltefosine has only been recently approved in India and its effectiveness in the field and the development of resistance are unknown. However, experience with antibiotics, including antibacterials, antifungals, and antivirals, indicates that resistance to currently-used drugs is the rule rather than the exception; this necessitates the continued search for new drugs. Particularly useful and missing from the armamentarium of treatment is prevention by an efficacious and safe pan-Leishmania vaccine. Our long-term goal is the identification and development of vaccines for the prevention or treatment of a number of human infectious diseases, including those caused by Leishmania. In this SBIR Phase I, we will test the efficacy of several putative antigens, delivered in a novel way, in protecting against infection by L. major. We will accomplish this in two specific aims: Aim One: Engineer yeast cells to express each of four candidate proteins using recombinant DNA technology. Aim Two: Test the in vivo efficacy of each vaccine formulation to protect vaccinated animals against a challenge of L. major. This work will be a prelude to further work in Phase II that will include testing for in vivo efficacy of each successful vaccine candidate in several Leishmania infection models as well as the detailed understanding of the immune response of each formulation. We believe that this work will lead to the development of prophylactic and therapeutic vaccines against Leishmania