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A novel vaccine against Leishmania

一种针对利什曼原虫的新型疫苗

基本信息

批准号：
6932638
负责人：
Claude P Selitrennikoff
金额：
$ 10万
依托单位：
MYCOLOGICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-05-15 至 2005-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6932638
关键词：
Leishmania Leishmania major Saccharomyces cerevisiae bioengineering /biomedical engineering biotechnology disease /disorder prevention /control immune response laboratory mouse leishmaniasis open reading frames polymerase chain reaction protozoal vaccine recombinant DNA vaccine development vaccine evaluation vector vaccine

项目摘要

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

描述（由申请方提供）：利什曼原虫是由白蛉白蛉传播的典型原虫，引起利什曼病。利什曼病影响着88个国家的1200万人，估计有3.5亿人面临感染不同种类利什曼原虫的风险。每年的新病例约为200万。像许多其他热带疾病一样，利什曼病与经济发展和人为的环境变化有关，这些变化增加了对白蛉病媒的接触。这种疾病对美国来说很重要，因为许多在伊拉克和阿富汗服役的退伍军人接触到白蛉，并患有利什曼病。利什曼原虫/艾滋病毒合并感染正在成为一种极其严重的新疾病，并且频率正在增加。治疗主要基于五价锑化合物，尽管一种新药米替福新在治疗利什曼病方面显示出希望。不幸的是，锑化合物是有毒的，并且在各种流行地区的抗性是常见的。米替福新最近才在印度获得批准，其在该领域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）的使用经验表明，对当前使用的药物产生耐药性是普遍现象，而不是例外;这就需要继续寻找新药。特别有用的和缺少的医疗设备的治疗是预防一个有效的和安全的泛利什曼原虫疫苗。我们的长期目标是鉴定和开发疫苗，用于预防或治疗一些人类传染病，包括由利什曼原虫引起的疾病。在SBIR的第一阶段，我们将测试几种假定的抗原，以一种新的方式提供，在保护免受感染的L。少校我们将在两个具体目标中实现这一目标：目标一：利用重组DNA技术，工程酵母细胞表达四种候选蛋白中的每一种。目的二：测试每种疫苗制剂的体内功效，以保护接种疫苗的动物免受L.少校这项工作将是第二阶段进一步工作的前奏，第二阶段将包括在几种利什曼原虫感染模型中测试每种成功候选疫苗的体内效力，以及详细了解每种制剂的免疫应答。我们相信，这项工作将导致利什曼原虫的预防性和治疗性疫苗的发展