Host factors impacting the innate response in humans to the candidate adjuvants RC529 and monophosphoryl lipid A.
Host factors impacting the innate response in humans to the candidate adjuvants RC529 and monophosphoryl lipid A.
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影响人类对候选佐剂 RC529 和单磷酰脂质 A 的先天反应的宿主因素。
DOI：
10.1016/j.vaccine.2003.10.019
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发表时间：
2004
期刊：
影响因子：
5.5
通讯作者：
D. D. Duncan
中科院分区：
文献类型：
--
作者：
L. Tiberio;L. Fletcher;J. Eldridge;D. D. Duncan
本研究的目的是确定某些基因型是否与候选疫苗佐剂RC529和单磷脂A(MPL)以及细菌内毒素(一种结构相似的控制刺激)的不同反应有关。在这项研究中，我们对+896个TLR4多态和选定的细胞因子多态进行了基因分型，并与供者性别一起用来模拟细胞因子对RC529、MPL和脂多糖的体外反应。我们的证据表明，这三种刺激中的每一种都与人类TLR4结合，每一种刺激在男性中的反应都比女性更高，并且TLR4在血液单核细胞中的表达水平在男性比女性更高。在全血化验中，74%到92%的反应变异是在受试者之间，然而多因素分析只解释了研究内变异的3%到18%。潜在地存在性别依赖的TLR4效应，因为在多因素模型中对某些反应存在显著的性别-TLR4交互作用项。由于我们分析的基因类型在研究中的影响很小，我们预计+896个TLR4基因和本研究中分析的其他因素在决定对TLR4参与的刺激的总体反应方面只有递增的影响。
The aim of this study was to determine if certain genotypes might be associated with variable responses to the candidate vaccine adjuvants RC529 and monophosphoryl lipid A (MPL), as well as to bacterial LPS, a structurally similar control stimulus. In this study, the +896 TLR4 polymorphism and selected cytokine polymorphisms were genotyped, and together with the donor sex, these factors were used to model the in vitro cytokine responses to RC529, MPL, and LPS. We show evidence that each of the three stimuli engage human TLR4, that each gave higher responses in men than women, and that TLR4 expression levels in blood monocytes were higher in men than women. From 74 to 92% of the response variation in the whole blood assay was between subjects, yet the multifactorial analyses accounted for only 3–18% of the variation within the study. Potentially there was a sex-dependent TLR4 effect since there was a significant sex-TLR4 interaction term in the multifactorial model for some responses. Since the genotypes we analyzed had such a modest impact in the study, we anticipate that +896 TLR4 genotype and the other factors analyzed in this study have only incremental effects in determining the overall response to TLR4-engaging stimuli.
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DOI：
10.1097/00002371-199112000-00002
发表时间：
1991
期刊：
Journal of immunotherapy : official journal of the Society for Biological Therapy
影响因子：
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DOI：
10.1073/pnas.250476497
发表时间：
2000-12-05
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11.1
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Aderem, A
DOI：
10.1165/ajrcmb.20.5.3494
发表时间：
1999-05-01
影响因子：
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作者：
Baldini, M;Lohman, IC;Martinez, FD
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Martinez, FD
DOI：
10.1073/pnas.97.19.10483
发表时间：
2000-09-12
影响因子：
11.1
作者：
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通讯作者：
Liggett, SB
影响因子：
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作者：
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通讯作者：
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