A Phase 1 trial of PfCP2.9: An AMA1/MSP1 chimeric recombinant protein vaccine for Plasmodium falciparum malaria
A Phase 1 trial of PfCP2.9: An AMA1/MSP1 chimeric recombinant protein vaccine for Plasmodium falciparum malaria
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DOI：
10.1016/j.vaccine.2008.09.081
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发表时间：
2008-12-09
期刊：
影响因子：
5.5
通讯作者：
Cao, Zhifang
中科院分区：
文献类型：
--
作者：
Malkin, Elissa;Hu, Jinhong;Cao, Zhifang
将顶膜抗原1(AMA1)和裂殖子表面蛋白1(MSP1)作为重组融合蛋白，用Montanide ISA 720佐剂配制而成，目的是复制寄生虫蛋白中存在的结构。先前对这种结构的试验表明，该疫苗是安全的和免疫原性的，但与注射部位的反应性有关。在第一阶段，PfCP2.9/Montanide ISA 720进行了一项近距离逐步升级的双盲随机对照试验，以评估替代剂量水平和疫苗接种计划，使用的是经过更深入和频繁的质量控制和稳定性分析的预制疫苗。这项试验是在2006年1月至2007年1月期间在70名健康的未患疟疾的中国志愿者中进行的。目的：评价PfCP2.9/ISA720在2种不同方案下5、20和50mgPfCP2.9/ISA 720的安全性、反应性和免疫原性。最常见的不良反应是注射部位压痛(53%)。在两种疫苗接种计划中，不良事件的频率和严重程度是相似的。在接受疫苗(p<；0.001)的志愿者中，整个研究过程中都诱导了抗体反应并保持升高，尽管通过ELISA检测到针对PfCP2.9免疫原的高抗体效价，但这些抗体的生物学功能并不能通过体外抑制寄生虫生长来反映，而且免疫荧光试验中对固定寄生虫的识别有限。在所有三种剂量水平和两种方案下，PfCP2.9/ISA 720的这种制剂具有良好的耐受性、安全性和免疫原性；但没有观察到针对寄生虫的功能性活性。(C)2008爱思唯尔有限公司。保留所有权利。
Apical Membrane Antigen 1 (AMA1) and Merozoite Surface Protein 1 (MSP1) were produced as a recombinant fusion protein and formulated with the adjuvant Montanide ISA 720 with the aim of replicating the structure present in the parasite protein. A previous trial with this construct demonstrated the vaccine was safe and immunogenic but was associated with injection site reactogenicity. This Phase I a close-escalating, double blind, randomized, controlled trial of PfCP2.9/Montanide ISA 720 was conducted to evaluate alternative dose levels and vaccination schedules, with a pre-formulated vaccine that had undergone more in-depth and frequent quality control and stability analysis. The trial was conducted in seventy healthy Chinese malaria-naive Volunteers between January 2006 and January 2007. The objective was to assess the safety, reactogenicity and immunogenicity of 5, 20 and 50 mu g of PfCP2.9/ISA 720 under 2 different schedules. The most common adverse event was injection site tenderness (53%). The frequency and severity of adverse events was similar in both vaccination schedules. Antibody responses were induced and remained elevated throughout the study in volunteers receiving vaccine (p < 0.001), Although high antibody titers as measured by ELISA to the PfCP2.9 immunogen were observed, biological function of these antibodies was not reflected by the in vitro inhibition of parasite growth, and there was limited recognition of fixed parasites in in immunofluorescence assay. At all three dose levels and both schedules, this formulation of PfCP2.9/ISA 720 is well tolerated, safe and immunogenic; however no functional activity against the parasite was observed. (C) 2008 Elsevier Ltd. All rights reserved.