Schistosome vaccine testing: lessons from the baboon model
Schistosome vaccine testing: lessons from the baboon model
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DOI：
10.1590/s0074-02762006000900061
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发表时间：
2006-10-01
期刊：
影响因子：
--
通讯作者：
Kariuki, Thomas M
中科院分区：
文献类型：
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作者：
Coulson, Patricia S;Kariuki, Thomas M
辐射减毒的核糖体疫苗在啮齿动物和灵长类动物中引起的高水平保护给人带来了希望，即依赖于等效机制的人类疫苗是可行的。在人类中，疫苗无疑将被施用于先前或目前感染的个体。因此，我们使用橄榄狒狒来研究疫苗诱导的免疫力是否会受到病毒感染的影响。我们发现，无论是先前的感染，终止化疗，也没有持续的慢性感染影响的保护水平。虽然IgM对疫苗接种或感染的反应是短暂的，但IgG反应随着每次连续暴露于疫苗而上升。这种上升被已经感染的动物对卵沉积的反应所掩盖。在人体试验中，有必要使用感染强度的间接估计来确定疫苗的效力。使用蠕虫负荷作为确定性标准，我们证明了替代措施，粪便卵和循环抗原，一贯高估保护。替代参数对蠕虫负荷的回归分析表明，高估的主要原因是测定的阈值灵敏度。如果我们将我们的发现外推到人类曼氏血吸虫病，很明显，未来的疫苗试验需要更敏感的感染强度间接测量。
The high level of protection elicited in rodents and primates by the radiation-attenuated schistosome vaccine gives hope that a human vaccine relying on equivalent mechanisms is feasible. In humans, a vaccine would be undoubtedly administered to previously or currently infected individuals. We have therefore used the olive baboon to investigate whether vaccine-induced immunity is compromised by a schistosome infection. We showed that neither a preceding infection, terminated by chemotherapy, nor an ongoing chronic infection affected the level of protection. Whilst IgM responses to vaccination or infection were short-lived, IgG responses rose with each successive exposure to the vaccine. Such a rise was obscured by responses to egg deposition in already-infected animals. In human trials it would be necessary to use indirect estimates of infection intensity to determine vaccine efficacy. Using worm burden as the definitive criterion, we demonstrated that the surrogate measures, fecal eggs, and circulating antigens, consistently overestimated protection. Regression analysis of the surrogate parameters on worm burden revealed that the principal reason for overestimation was the threshold sensitivity of the assays. If we extrapolate our findings to human schistosomiasis mansoni, it is clear that more sensitive indirect measures of infection intensity are required for future vaccine trials.