VACCINE INDUCED IMMUNE RESPONSES TO PLASMODIAL ANTIGENS

描述：(改编自申请者摘要)对人类的广泛研究 动物模型表明，对疟疾的获得性免疫力会增强。然而， 减少疟疾发病率和死亡率的目标是通过 尚未实现免疫接种。我们为鉴定疟原虫抗原所做的努力 触发保护性反应的物质主要集中在体内的 免疫诱导保护。使用这个约氏疟原虫模型，我们 鉴定了一个新的裂殖子表面抗原和一个独特的抗原家族 由受感染的红细胞分泌。我们提供了他们接种疫苗的证据 约氏疟原虫模型中的潜力及其在疟原虫中的保守性 恶性疟原虫。此应用程序的目的是评估 用这些保护性抗原的保守结构域进行免疫。这个 假说是分泌性血液阶段的色氨酸富集区(WRD) 疟疾抗原及其表皮生长因子样结构域的研究 裂殖子表面蛋白-6(MSP-6)是保护性免疫反应的靶标。 PYWRD和pYMSP-6保守区的免疫效果 将对抗原进行测量，以预防血液期约氏疟原虫疟疾。 疫苗配方和输送系统将被操纵，以优化 重组约氏疟原虫WRD和MSP-6免疫诱导的保护性研究 抗原与裂殖子表面蛋白-1结合使用。T细胞 和与免疫诱导的保护相关的B细胞反应 结合表达WRD和EGF样结构域的约氏杆菌抗原 将会被定义。因为约氏疟原虫对这些区域的免疫反应 模型的特征，研究结果将直接应用于P. 恶性疟原虫。提高兔抗重组pfWRD和pfWRD抗体的能力 将评价pfMSP-6对恶性疟原虫体外生长的抑制作用。 使用集成方法，新的血液阶段疫苗靶标可以 有效配方组合，提高免疫效力 将被描述为。研究结果将为规划提供逻辑基础 以及评估多价血液阶段疫苗的人体试验，该疫苗包括 这些恶性疟原虫抗原的WRD和EGF样结构域。

DESCRIPTION: (Adapted from Applicant's Abstract) Extensive studies in humans and animal models indicate that acquired immunity to malaria develops. Yet, the goal of reducing morbidity and mortality due to malaria through active immunization has not been achieved. Our efforts to identify plasmodial antigens that trigger protective responses are focused on an in vivo system of immunization-induced protection. Using this Plasmodium yoelii model, we identified a novel merozoite surface antigen and a unique family of antigens secreted from infected erythrocytes. We provided evidence of their vaccine potential in the P. yoelii model and of their conservation in Plasmodium falciparum. The objective of this application is to evaluate the efficacy of immunization with conserved domains of these protective antigens. The hypothesis is that the tryptophan-rich domain (WRD) of secreted blood-stage malarial antigens and the epidermal growth factor (EGF)-like domains of merozoite surface protein-6 (MSP-6) are targets of protective immune responses. The efficacy of immunization with conserved domains of pyWRD and pyMSP-6 antigens will be measured as protection against blood-stage P. yoelii malaria. Vaccine formulations and delivery systems will be manipulated to optimize protection induced by immunization with recombinant P. yoelii WRD and MSP-6 antigens administered in combination with merozoite surface protein -1. T cell and B cell responses that correlate with protection induced by immunization with combinations of P. yoelii antigens expressing WRD and EGF-like domains will be defined. As the immune responses to these domains in the P. yoelii model are characterized, the findings will be directly applied to studies of P. falciparum. The ability of rabbit antisera raised against recombinant pfWRD and pfMSP-6 to inhibit the in vitro growth of P. falciparum will be evaluated. Using an integrated approach, novel blood-stage vaccine targets that can be effectively formulated in combination to increase the efficacy of immunization will be characterized. The results will provide a logical basis for planning and evaluating human trials of a multivalent, blood-stage vaccine that includes the WRD and EGF-like domains of these P. falciparum antigens.