STUDIES ON THE IMMUNOBIOLOGY OF MALARIA

免疫力，提供保护，防止疾病的发病率和死亡率 人们对疟疾仍然知之甚少。同样，免疫反应 在动物模型中介导亚单位疫苗的保护性免疫 目前也不清楚。在缺乏可靠的体外相关性的情况下 在缺乏对什么的充分了解的情况下 有助于对疟疾的免疫力，发展有效的疟疾 疫苗将继续是最好的随意性。这次会议的主要目标是 该项目旨在诱导并定义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获得了保护性免疫 用主要表面蛋白MSP1免疫两种啮齿动物(P。 和灵长类动物(Aotus猴的恶性疟原虫)模型。 尽管这些模型系统中的免疫可能是抗体依赖的，但它 看来，单靠抗体，如用酶联免疫吸附试验检测，并不能起到调节作用。 保护豁免权。已经进行了各种体外试验。 探讨该亚单位疫苗诱导保护性的机制 豁免权。疟疾全寄生虫和沙门氏菌疫苗接种 在小鼠中引起对P.vinckei的保护免疫。这件事的豁免权 动物模型系统主要由细胞介导，依赖于CD4+T细胞 而且还需要脾。我们正在利用这个模型来研究 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鉴定疟疾 导致保护性的寄生虫多肽(T细胞表位)。自.起 1996年1月，该项目将终止，任何正在进行的和未来的 研究将整合到重组蛋白的表达中 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.