Physicochemical characterization and biological activity of synthetic TLR4 agonist formulations
Physicochemical characterization and biological activity of synthetic TLR4 agonist formulations
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DOI：
10.1016/j.colsurfb.2009.08.022
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发表时间：
2010-01-01
影响因子：
5.8
通讯作者：
Vedvick, Thomas S.
中科院分区：
文献类型：
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作者：
Anderson, Ryan C.;Fox, Christopher B.;Vedvick, Thomas S.
免疫刺激分子如单磷酰脂质A（MPL），一种Toll样受体4（TLR 4）激动剂，可以配制成增强疫苗佐剂作用和促进Th 1型免疫应答。本研究比较了含有合成MPL类似物的水性和乳液制剂的体外和体内效力。此外，制剂结构和合成TLR-4激动剂和抗原与制剂的结合使用动态光散射、ζ电位测量来表征。高效液相色谱法和SDS-PAGE检测了用来自动物、植物和合成来源的不同油和表面活性剂组分配制激动剂的生物学和生物物理学效应。这些发现对于TLR 4激动剂的配制以及制剂组分替代对佐剂活性的影响具有重要意义。结果表明（1）激动剂与乳剂制剂中的油滴相关，（2）含有合成的TLR 4激动剂的乳剂制剂比水性制剂或不含激动剂的乳剂制剂诱导更高的IgG 2a/IgG 1抗体比率。和（3）适当的植物来源的组分可以替代水包油乳剂中的动物来源的组分而不损失生物活性（C）2009 Elsevier B.V保留所有权利。
Immunostimulatory molecules such as monophosphoryl lipid A (MPL), a Toll-like receptor 4 (TLR4) agonist, can be formulated to enhance vaccine adjuvant effects and to promote a Th1-type immune response This study compares the in vitro and in vivo potency of aqueous and emulsion formulations containing a synthetic MPL analogue In addition, formulation structure and association of the synthetic TLR-4 agonist and antigen with the formulation are characterized using dynamic light scattering, zeta potential measurement. HPLC. and SDS-PAGE The biological and biophysical effects of formulating the agonist with different oil and surfactant components from animal, plant, and synthetic sources ale examined These findings have important implications for the formulation of TLR4 agonists as well as the Influence of formulation component substitution on adjuvant activity The results indicate that (1) the agonist is associated with the oil droplets in emulsion formulations, (2) the emulsion formulations containing synthetic TLR4 agonist Induce higher IgG2a/IgG1 antibody ratios than aqueous formulations or an emulsion formulation without the agonist. and (3) appropriate plant-derived components can be substituted for animal-derived components in oil-in-water emulsions without loss of biological activity (C) 2009 Elsevier B.V All rights reserved.