Safety, Immunogenicity and Efficacy of Vaccine

基于恶性疟原虫顶膜抗原1或AMA-1的候选血液期疟疾疫苗与葛兰素史克生物制剂的佐剂AS02A(一种免疫增强剂)相结合的1B期和2B期候选疫苗将在西非马里班加卡拉的儿童身上进行。该项目对于开发一种安全有效的疟疾疫苗以预防非洲婴儿和儿童的疾病和死亡的总体规划目标至关重要。在这些临床试验中获得的血液样本将接受项目2研究计划中描述的分子和免疫学分析。那些 分析将提供关于毒株特异性保护与交叉反应保护、免疫反应的持续时间以及自然增强的影响的信息，所有这些都将为进一步的疫苗开发工作提供信息，包括确定哪些成分最适合包括在多组分疫苗中。马里的一项儿科1B期研究将比较三种不同剂量的AMA-1/AS02A。疟疾疫苗或对照疫苗将在0、1和2个月时以交错、剂量递增的方式注射，以评估疫苗的安全性及其在儿童中产生免疫反应的能力。根据这项试验的结果，将为AMA-1疗效的2B阶段研究选择最佳疫苗剂量水平。这项2B期儿童双盲对照试验将确定疟疾疫苗是否安全、免疫原性和在预防疟疾疾病和感染方面是否有效。有效疟疾疫苗的最大公共卫生目标是减少儿童的疾病和死亡，特别是在非洲。拟议的研究将评估疫苗减轻疟疾感染和疾病的能力，从而评估其单独或作为多抗原疟疾疫苗组成部分的潜力。如果成功，这种疫苗可能会进一步开发为独立疫苗或与 其他保护性疟疾抗原和/或AMA-1基因类型。一种既能预防疟疾感染又能预防疟疾的疫苗不仅会让非洲儿童受益，也会让前往疟疾流行地区的旅行者受益，从而提供一个市场，为疟疾流行地区使用的疫苗提供补贴。

Definitive Phase 1B and Phase 2B trials of a candidate blood stage malaria vaccine based on Plasmodium falciparum apical membrane antigen 1, or AMA-1, in combination with GlaxoSmithKline Biologicals' adjuvant AS02A, an immune boosting agent, will be conducted in children in Bandiagara, Mali, West Africa. This project is central to the overall program goal of developing a safe and effective malaria vaccine that prevents disease and death in African infants and children. Blood samples obtained in these clinical trials will be subject to the molecular and immunological analyses described in the Project 2 Research Plan. Those analyses will provide information on strain-specific vs. cross-reactive protection, duration of immune response, and the impact of natural boosting, all of which will inform further vaccine development efforts, including determining which components would be best to include in a multi-component vaccine. A pediatric Phase 1B study in Mali will compare three different doses of AMA-1/AS02A. The malaria vaccine or a comparator vaccine will be injected at 0, 1, and 2 months in a staggered, dose escalating fashion to evaluate safety of the vaccine and its ability to produce an immune response in children. Based on the results of this trial, the best vaccine dose level will be chosen for a Phase 2B study of AMA-1 efficacy. This Phase 2B double blind, controlled trial in children will determine if the malaria vaccine is safe, immunogenic and effective at preventing malaria disease and infection. The greatest public health goal for an effective malaria vaccine is to reduce disease and death in children, particularly in Africa. The proposed studies will evaluate the ability of the vaccine to mitigate malaria infection and disease and thus estimate its potential either alone or as a component of a multi-antigen malaria vaccine. If successful, this vaccine may be further developed as a stand-alone vaccine or combined with other protective malaria antigens and/or AMA-1 genotypes. A vaccine that provides protection against both malaria infection and malaria disease will benefit not only African children but also travelers to malaria endemic regions, providing a market to subsidize a vaccine for use in the malaria endemic world.