STUDIES ON THE IMMUNOBIOLOGY OF MALARIA

提供保护以防止疾病和死亡的免疫力 对疟疾的了解仍然很少。 同样，免疫反应， 在动物模型中介导对亚单位疫苗接种的保护性免疫， 目前也不清楚。 在缺乏可靠的体外相关因素的情况下 保护性免疫力，以及缺乏充分了解 有助于对疟疾的免疫力，发展有效的疟疾疫苗， 疫苗最多也只能是随机的。 本项目的主要目标是 项目是引出并确定针对疟疾的保护性免疫 在动物模型中。 我们现在已经通过亚单位引发了保护性免疫 在两种啮齿动物中用主要表面蛋白MSP 1接种（P. 小鼠中的约氏疟原虫）和灵长类动物（Aotus猴中的恶性疟原虫）模型。 虽然这些模型系统中的免疫可能是抗体依赖性的，但它 通过ELISA测量，似乎单独的抗体不介导 保护性免疫 已经进行了各种体外试验 探讨该亚单位疫苗诱导的保护作用机制 免疫力 接种完整疟原虫和沙门氏菌 增强了小鼠对P.vinckei的保护性免疫力。 这件事的豁免权 动物模型系统主要是细胞介导的，CD4+ T细胞依赖的 需要脾脏 我们用这个模型来研究 脾在提供保护性免疫方面的贡献， 结合重组沙门氏菌和卡介苗，以识别疟疾 寄生虫多肽（T细胞表位），导致保护。 截至 1996年1月，该项目将终止，任何正在进行的和未来的 研究将纳入重组蛋白表达 单位

Immunity that provides protection against the morbidity and mortality of malaria remains poorly understood. Likewise, the immune responses that mediate protective immunity to subunit vaccination in animal models is also presently unclear. In the absence of reliable in vitro correlates of protective immunity and with the lack of a full understanding of what contributes to immunity to malaria, development of effective malaria vaccines will continue to be haphazard at best. The major goals of this project are to elicit and then define protective immunity against malaria in animal models. We have now elicited protective immunity by subunit vaccination with the major surface protein, MSP1, in both rodent (P. yoelii in mice) and primate (P. falciparum in Aotus monkeys) models. Although immunity in these model systems may be antibody-dependent, it appears that antibodies alone, as measured by ELISA, do not mediate protective immunity. A variety of in vitro assays have been undertaken to search for the mechanisms of this subunit vaccine-induced protective immunity. Vaccination with whole malaria parasites and Salmonella elicits protective immunity to P. vinckei in mice. The immunity in this animal model system is primarily cellular-mediated, CD4+ T cell-dependent and requires the spleen. We are using this model to study the contribution of the spleen in providing protective immunity and, in conjunction with recombinant Salmonella and BCG, to identify malaria parasite polypeptides (T cell epitopes) that lead to protection. As of January 1996, this project will terminate and any ongoing and future studies will be incorporated into the Recombinant Protein Expression Unit.