VACCINE INDUCED IMMUNE RESPONSES TO PLASMODIAL ANTIGENS

描述：（改编自申请人摘要）在人类中的广泛研究 动物模型表明，对疟疾的获得性免疫会发展。然而 减少疟疾发病率和死亡率的目标， 免疫尚未实现。我们鉴定疟原虫抗原的努力 触发保护性反应的机制主要集中在体内系统， 免疫诱导保护。使用约氏疟原虫模型，我们 鉴定了一种新的裂殖子表面抗原和一个独特的抗原家族 从受感染的红细胞中分泌出来我们提供了他们疫苗的证据 在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。本申请的目的是评价 用这些保护性抗原的保守结构域进行免疫。的 一种假说认为，分泌性血液阶段的富含色氨酸的结构域（WRD） 疟疾抗原和表皮生长因子（EGF）样结构域 裂殖子表面蛋白-6（MSP-6）是保护性免疫应答的靶标。 用pyWRD和pyMSP-6的保守结构域免疫的功效 抗原将被测量为对血液阶段约氏疟原虫疟疾的保护。 疫苗配方和输送系统将被操纵，以优化 用重组约氏疟原虫WRD和MSP-6免疫诱导的保护 抗原与裂殖子表面蛋白-1联合给药。T细胞 和与免疫诱导的保护相关的B细胞应答 与表达WRD和EGF样结构域的约氏疟原虫抗原的组合 将被定义。由于约氏疟原虫中对这些结构域的免疫应答， 模型的特点，研究结果将直接应用于研究P。 恶性疟原虫。重组pfWRD和pfWRD的兔抗血清的免疫原性和特异性均较好。 将评价pfMSP-6抑制恶性疟原虫体外生长的作用。 使用一种综合方法，新的血液阶段疫苗的目标，可以 有效地组合配制以提高免疫效力 将被定性。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， 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.