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（由申请人提供）：利什曼原虫是通过静脉菌菌sand蝇传播的typanosomatid原生动物，导致利什曼病。利什曼病影响88个国家的1200万人，估计有3.5亿人有利什曼尼亚种类感染的风险。新病例的年发病率约为200万。像许多其他热带疾病一样，利什曼尼亚人与经济发展和人造环境变化有关，这增加了对砂蝇载体的接触。由于许多在伊拉克和阿富汗退伍军人的士兵暴露于沙蝇，并患有利什曼病。利什曼原虫/艾滋病毒共同感染正在成为一种非常严重的新疾病，频率正在增加。治疗主要基于五价锑化合物，尽管一种新药Miltefosine显示出对治疗利什曼病的有希望。不幸的是，锑化合物具有毒性，并且在各个地方性地区的耐药性很常见。米尔特法辛（Miltefosine）最近才在印度获得批准，其在该领域的有效性且抵抗的发展尚不清楚。但是，抗生素的经验，包括抗菌药物，抗真菌剂和抗病毒药，表明对当前使用的药物的耐药性是规则而不是例外。这需要继续寻找新药。治疗的武术特别有用和缺失是一种有效且安全的泛利什曼菌疫苗的预防。我们的长期目标是鉴定和开发用于预防或治疗多种人类感染性疾病（包括利什曼尼亚引起的疫苗）。在SBIR第一阶段，我们将测试以新颖方式递送的几种推定抗原的功效，以防止L. Major的感染。我们将在两个具体的目标中实现这一目标：目标一个：工程酵母细胞使用重组DNA技术表达四种候选蛋白的每一种。目标二：测试每种疫苗配方的体内功效，以保护疫苗的动物免受乳杆菌的挑战。这项工作将是在第二阶段进一步工作的序幕，其中包括测试在几种利什曼尼亚感染模型中每个成功疫苗候选者的体内功效，以及对每种配方免疫反应的详细理解。我们认为，这项工作将导致针对利什曼尼亚的预防性和治疗性疫苗的开发