MOLECULAR STRATEGIES TOWARDS A COCCIDIOIDOMYCOSIS VACCIN

总体描述（改编自应用）：球孢子菌病是一种 美国西南部的一种重要传染病， 发病率和死亡率相当高。根据皮肤测试转换， 估计每年有25，000至100，000例新感染。发生率 播散性（肺外）感染在妊娠期很高， 免疫抑制，和一些种族群体。第二次感染是 非常罕见，这表明自然免疫是有效的。的 研究人员发现了两种蛋白质，赋予保护性免疫力， 小鼠感染模型。一种是细胞质酶，用这种酶免疫 蛋白质导致每单位微生物数量减少10至50倍。 肺。这些结果提供了一种有效的疫苗的概念证明， 粗球孢子菌是一个现实的目标。该计划包括五个 项目项目I侧重于抗原鉴定、表达和 初步测试。项目II将评估PRA作为保护性抗原， 详细目标是确定PRA中的T细胞表位， 比PRA更有效的疫苗。项目三将调查关键类型 使用基因敲除小鼠， 有针对性的免疫缺陷。项目四将评估遗传多样性 梭免疫球蛋白这个项目的目标是确定多态性 潜在的候选疫苗是在DNA序列和表达水平。 项目五将测试抗原，佐剂，和输送系统， 小鼠模型中的保护性免疫。在项目V（和项目I）中， Neil Ampel计划测试抗原引发T细胞反应的能力 皮肤测试呈阳性的人。这两个核心旨在提供蛋白质 核心A）和行政支助（核心B）。这 计划是一个高度互动的，协调的，集中的努力，设计一个 疫苗，以保护小鼠免受实验性球孢子菌病。大量的 重点放在寻找佐剂和免疫方案， 转移到人类身上。研究人员还对定义 关键的免疫反应和体外免疫试验， 对感染有抵抗力。这些信息对于测试免疫力很重要。 这将是人类疫苗接种的关键一步。 球孢子菌病人用疫苗的评价方法。

OVERALL DESCRIPTION (Adapted from application): Coccidioidomycosis is an important infection in the Southwestern United States responsible for considerable morbidity and mortality. Based on skin test conversions, it is estimated that 25,000 to 100,000 new infections occur each year. The incidence of disseminated (extra-pulmonary) infection is high in pregnancy, the immunosuppressed, and some ethnic groups. Second infections are extraordinarily rare, indicating that natural immunity works. The investigators have found two proteins that confer protective immunity in a mouse model of infection. One is a cytoplasmic enzyme; immunization with this protein results in a 10 to 50-fold reduction in the number of organisms per lung. These results provide proof of concept that an effective vaccine for Coccidioides immitis is a realistic goal. The program consists of five projects. Project I focuses on antigen identification, expression, and preliminary testing. Project II will evaluate PRA as a protective antigen in detail. The goal is to define T-cell epitopes within PRA that might be more effective vaccines than PRA. Project III will investigate the critical types of lymphocytes and cytokines required for vaccination, using knock-out mice with targeted immune defects. Project IV will evaluate the genetic diversity of C. immitis. The goal of this project is to determine how polymorphic potential vaccine candidates are in the DNA sequence and level of expression. Project V will test antigens, adjutants, and delivery systems that provide protective immunity in the mouse model. Within Project V (and Project I) Dr. Neil Ampel plans to test antigens for their ability to elicit T-cell responses in skin test positive people. The two cores are designed to provide Protein and DNA to the projects (Core A) and administrative support (Core B). This program is a highly interactive, coordinated, and focused effort to design a vaccine to protect mice from experimental coccidioidomycosis. A great deal of emphasis is placed on finding adjuvants and immunization schemes that can be transferred to human beings. The investigators are also interested in defining the critical immune responses and in vitro tests of immunity that correlate with resistance to infection. This information is important to test the immune response to vaccination in people, which would be a crucial step in the evaluation process of a human vaccine for coccidioidomycosis.