Cheng Q, Lawrence G, Reed C, Stowers A, Ranford-Cartwright L, Creasey A, Carter R, Saul A
The Cooperative Research Centre for Vaccine Technology, Queensland Institute of Medical Research, Brisbane, Australia.
Am J Trop Med Hyg. 1997 Oct;57(4):495-500. doi: 10.4269/ajtmh.1997.57.495.
Several prototype vaccines against the asexual blood stage of malaria are undergoing preclinical and phase I testing. Although these vaccines have been chosen for their ability to elicit an anti-parasite response, no practical and sensitive clinical trial procedure has been available for measuring their impact on parasite growth. We describe a system that allows parasite growth rates to be measured in volunteers through the incubation period. Two necessary elements of this system are developed: suitable blood-stage Plasmodium falciparum inocula, and a highly sensitive and quantitative assay to measure parasite growth during the incubation period. We infected five nonimmune volunteers with an inoculum as small as 300 parasites and demonstrated that the resultant in vivo asexual parasite growth rates were reproducible at 12-15-fold per cycle. The system allowed the infection to be followed for eight days before treatment without symptoms developing. These findings suggest that it is feasible to directly measure the anti-parasite efficacy of a prototype malaria vaccine in human volunteers without subjecting them to the risk of disease.
几种针对疟疾无性血液阶段的原型疫苗正在进行临床前和I期试验。尽管这些疫苗因其引发抗寄生虫反应的能力而被选中，但尚无实用且灵敏的临床试验程序来衡量它们对寄生虫生长的影响。我们描述了一种系统，该系统能够在潜伏期内测量志愿者体内的寄生虫生长速率。该系统开发了两个必要要素：合适的血液阶段恶性疟原虫接种物，以及一种高度灵敏且定量的检测方法，用于测量潜伏期内的寄生虫生长。我们用低至300个寄生虫的接种物感染了5名非免疫志愿者，并证明由此产生的体内无性寄生虫生长速率在每个周期可重复达到12至15倍。该系统允许在治疗前对感染情况进行八天的跟踪，且未出现症状。这些发现表明，在不使人类志愿者面临患病风险的情况下，直接测量原型疟疾疫苗的抗寄生虫效力是可行的。
