Physicochemical characterization and biological activity of synthetic TLR4 agonist formulations

被引：85

作者：

Anderson, Ryan C. ^{[1
]}

Fox, Christopher B. ^{[1
]}

Dutill, Timothy S. ^{[1
]}

Shaverdian, Narek ^{[1
]}

Evers, Tara L. ^{[1
]}

Poshusta, Garrett R. ^{[1
]}

Chesko, James ^{[1
]}

Coler, Rhea N. ^{[1
]}

Friede, Martin ^{[2
]}

Reed, Steven G. ^{[1
]}

Vedvick, Thomas S. ^{[1
]}

机构：

[1] Infect Dis Res Inst, Seattle, WA 98104 USA

[2] WHO, Initiat Vaccine Res, CH-12211 Geneva 27, Switzerland

来源：

COLLOIDS AND SURFACES B-BIOINTERFACES | 2010年 / 75卷 / 01期

基金：

比尔及梅琳达.盖茨基金会;

关键词：

Vaccine adjuvant; Oil-in-water emulsion; Synthetic TLR4 agonist; Squalene; OIL-IN-WATER; BLOCK POLYMER SURFACTANTS; ADJUVANT ACTIVITY; DELIVERY-SYSTEM; PROTECTIVE EFFICACY; VACCINE ADJUVANTS; IMMUNE-RESPONSES; O/W EMULSION; MACROPHAGES; VITRO;

D O I：

10.1016/j.colsurfb.2009.08.022

中图分类号：

Q6 [生物物理学];

学科分类号：

071011 ;

摘要：

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.

引用

页码：123 / 132

页数：10

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