The immunomodulating properties of human respiratory syncytial virus and immunostimulating complexes containing Quillaja saponin components QH-A, QH-C and ISCOPREP™703

The immunomodulating properties of human respiratory syncytial virus and immunostimulating complexes containing Quillaja saponin components QH-A, QH-C and ISCOPREP™703
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DOI:
10.1016/j.femsim.2004.08.010
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发表时间:
2005-02-01
影响因子:
--
通讯作者:
Morein, B
Morein, B
中科院分区:
其他
文献类型:
--
作者:
Hu, KF;Regner, M;Morein, B

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一种针对人呼吸道合胞病毒(HRSV)的成功疫苗可能诱导Th1或平衡的Th1/Th2细胞因子反应。我们测试了一组含有不同皂树皂苷组分(QH - A、QH - C以及703:70% QH - A和30% QH - C的混合物)且具有不同免疫学特性的HRSV免疫刺激复合物(ISCOMs)诱导先天性和获得性免疫反应的能力。HRSV 703 ISCOMs诱导出最强的先天性和获得性免疫反应,其次是RSV QH - C和QH - A ISCOMs。所有三种配方都诱导了不同程度的Th1偏向性反应,其中干扰素 - γ的显著产生量比白细胞介素 - 4和白细胞介素 - 5高10 - 50倍。HRSV特异性IgG同种型图谱与Th1细胞因子的主要分泌相关,强烈诱导IgG2a抗体产生。703 ISCOMs诱导出最显著的Th1图谱,其次是QH - C和QH - A ISCOMs。与G蛋白相比,这些ISCOMs中F蛋白的高掺入量以及ISCOM的Th1偏向性可能是促进Th1型图谱的原因。鉴于ISCOM概念的多种特性,配制具有最佳Th1/Th2平衡的RSV ISCOM配方的前景可期。(C)2004欧洲微生物学会联合会。由爱思唯尔出版社出版。保留所有权利。
A successful vaccine against human RSV (HRSV) is likely to induce a Th1 or a balanced Th1/TH2 cytokine response. We tested a panel of HRSV immunostimulating complexes (ISCOMs) containing different Quillaja saponin fractions (QH-A, QH-C, and 703: a mixture of 70% QH-A and 30% QH-C) with different immunological properties for their capacity of inducing innate and acquired immune responses. The HRSV 703 ISCOMs induced the strongest innate and acquired immune responses, followed by RSV QH-C and QH-A ISCOMs. All three formulations induced various degrees of Th1 bias response with prominent production of IFN-gamma being 10-50 times higher than that of IL-4 and IL-5. The HRSV specific IgG isotype profile correlated with the predominant secretion of Th1 cytokines, with strong induction of IgG2a antibodies. The 703 ISCOMs induced the most pronounced Th1 profile followed by QH-C and QH-A ISCOMs. The high incorporation of F protein in these ISCOMs compared to G protein combined with the Th1 biased nature of ISCOM are likely to be the causes to promote a Th1 type of profile. The prospect to formulate an RSV ISCOM formulation with an optimal Th1/Th2 balance is in reach particularly in view of the versatile properties of the ISCOM concept. (C) 2004 Federation of European Microbiological Societies. Published by Elsevier B.V.. All rights reserved.