VACCINE INDUCED IMMUNE RESPONSES TO PLASMODIAL ANTIGENS

恶性疟原虫有效疫苗的研制 疟疾可以缓解最重要的公共卫生问题之一 世界性的问题。显然有必要确定新的疟原虫 能够对血液期疟疾产生保护作用的抗原。我们 已经采取了严格的基于免疫的方法来解决这个问题。vbl.使用 约氏疟原虫模型检测几种粗血期抗原和 佐剂组合，我们已经建立了疫苗诱导系统 对血液期疟疾感染的免疫力。提供可靠的保护，防止 已经实现了致命性和致死性的约氏肺孢子虫挑战感染。我们 构建了约氏疟原虫基因组文库和cDNA表达文库 根据免疫动物的免疫反应选择重组子 并保护其免受约氏疟原虫的感染。这件事的主要焦点是 建议将对入选的疫苗潜力进行评估 重组抗原，以及保护性疟原虫的详细分析 抗原和编码它们的基因。这一行动的具体目标 项目有1)测试从选定的cDNA中提纯的重组抗原 克隆人具有免疫小鼠抵抗非致命性和致命性的能力 约氏假单胞菌感染和异源挑战感染； 通过鉴定和鉴定保护性约氏杆菌抗原，详细描述保护性约氏杆菌抗原 定位其相应的天然蛋白质，通过获得其完整的- 并通过评估它们在基因序列中的可能功能 寄生虫的生物学；3)开始描述免疫反应 通过检测抗原特异性来保护约氏疟原虫抗原 T细胞产生细胞因子(IL-2、干扰素-γ、IL-4、IL-10)的研究 并获得了血清中抗原特异性抗体的同型图谱 来自保护性重组抗原免疫的小鼠，之前和 攻击性感染约氏原虫后。我们的长期目标是 利用所获得的信息克隆P. 恶性疟原虫，其目标是构建类似的多价血液- 针对人类疟疾的阶段疫苗。

The development of an effective vaccine against Plasmodium falciparum malaria could alleviate one of the most significant public health problems world-wide. There is clearly a need to identify new plasmodial antigens which can induce protection against blood-stage malaria. We have taken a strict immunization-based approach to this problem. Using the Plasmodium yoelii model to test several crude blood stage antigen and adjuvant combinations, we have established a system of vaccine induced immunity to blood-stage malaria infection. Solid protection against non- lethal and lethal P. yoelii challenge infection have been achieved. We have constructed P. yoelii genomic and cDNA expression libraries and selected recombinants based on the immune response of animals immunized and protected against P. yoelii infection. The major focus of this proposal will be the evaluation of the vaccine potential of selected recombinant antigens, and a detailed analysis of protective plasmodial antigens and the genes which encode them. The specific goals of this project are 1) to test purified recombinant antigens from selected cDNA clones for their ability to immunize mice against non-lethal and lethal P. yoelii infection as well as heterologous challenge infection; 2) to characterize protective P. yoelii antigens in detail, by identifying and localizing their corresponding native proteins, by obtaining their full- length gene sequence and by assessing their possible function in the biology of the parasite; 3) to begin to -characterize the immune response to protective P. yoelii antigens by determining the antigen specific profile of cytokine production (IL-2, IFN-gamma, IL-4, IL-10) by T cells and the isotypic profile of antigen specific antibodies in sera obtained from mice immunized with protective recombinant antigens, both before and after challenge infection with P. yoelii. Our long term objective is to use the information gained to clone homologous antigen genes from P. falciparum, with the goal of constructing a similar multivalent blood- stage vaccine against human malaria.