Development of Pre-Erythrocytic Malaria Vaccines

今年的主要发现如下。 1.表明，放射减毒子孢子静脉注射到NHP诱导有效的CD 4和CD 8 + T细胞反应的血液和肝脏。确定肝脏中高频率的NK细胞响应于刺激而分泌IFN-γ，从而提供额外的效应细胞用于保护。 单核细胞和树突状细胞可将SPZ抗原呈递给T细胞。 2.证明了新型全长恶性疟原虫CSP蛋白在小鼠中引发有效的CD 4 + T细胞和体液免疫，足以在攻击后限制体内寄生虫复制。 3.启动了一项I期临床试验，在剂量递增研究中评估通过IV途径给予的辐照PfSPZ是否安全和具有保护作用。

The major discovery this year are as follows. 1. Showed that radiation attenuated sporozoites administered intravenously into NHP induced potent CD4 and CD8+ T cell responses in blood and liver. Established that a high frequency of NK cells in the liver secrete IFN-g in response to stimulation providing an additional effector cell for protection. Furthermore, showed that monocytes and dendritic cells present SPZ antigen to T cells. 2. Demonstrated that a novel full length P. falciparum CSP protein elicited potent CD4+ T cell and humoral immunity in mice sufficient to limit parasite replication in vivo following challenge. 3. Initiated a phase I clinical trial assessing whether irradiated PfSPZ given by the IV route is safe and protective in a dose escalation study.