VACCINE INDUCED IMMUNE RESPONSES TO PLASMODIAL ANTIGENS

恶性疟原虫有效疫苗的研制 疟疾可以缓解人类最严重的公共卫生问题之一， 全世界的问题。很明显，有必要确定新的疟原虫 可以诱导针对血液阶段疟疾的保护的抗原。我们 对这个问题采取了严格的基于免疫的方法。使用 约氏疟原虫模型用于测试几种粗制的血液阶段抗原， 佐剂组合，我们已经建立了一个疫苗诱导的系统， 对血液阶段疟疾感染的免疫力坚固的防护， 已经实现了致死性和致死性约氏疟原虫攻击感染。我们 构建了约氏疟原虫基因组和cDNA表达文库， 基于免疫动物的免疫应答选择重组体 并防止约氏疟原虫感染。这其中的主要焦点 建议将是对选定的疫苗潜力的评价， 重组抗原，并详细分析了保护性疟原虫 抗原及其编码基因。具体目标是 项目是1）测试来自选择的cDNA的纯化的重组抗原 克隆，因为它们能够免疫小鼠， 约氏疟原虫感染以及异源攻击感染; 2） 通过鉴定和鉴定保护性约氏疟原虫抗原， 定位其相应的天然蛋白质，通过获得其完整的， 长度的基因序列，并通过评估它们在 寄生虫的生物学; 3）开始表征免疫应答 保护性约氏疟原虫抗原， T细胞产生细胞因子（IL-2、IFN-γ、IL-4、IL-10）的概况 以及获得的血清中抗原特异性抗体的同种型谱 来自用保护性重组抗原免疫的小鼠， 在攻击感染约氏疟原虫后。我们的长远目标是 利用所获得的信息克隆P. 恶性疟原虫，目的是构建一个类似的多价血液- 针对人类疟疾的阶段性疫苗。

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.