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Adsorption of a synthetic TLR7/8 ligand to aluminum oxyhydroxide for enhanced vaccine adjuvant activity: A formulation approach.

Adsorption of a synthetic TLR7/8 ligand to aluminum oxyhydroxide for enhanced vaccine adjuvant activity: A formulation approach.
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Fox CB, Orr MT, Van Hoeven N, Parker SC, Mikasa TJ, Phan T, Beebe EA, Nana GI, Joshi SW, Tomai MA, Elvecrog J, Fouts TR, Reed SG,


Fox CB, Orr MT, Van Hoeven N, Parker SC, Mikasa TJ, Phan T, Beebe EA, Nana GI, Joshi SW, Tomai MA, Elvecrog J, Fouts TR, Reed SG, (click to view)

Fox CB, Orr MT, Van Hoeven N, Parker SC, Mikasa TJ, Phan T, Beebe EA, Nana GI, Joshi SW, Tomai MA, Elvecrog J, Fouts TR, Reed SG,

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Journal of controlled release : official journal of the Controlled Release Society 2016 11 12244(Pt A) 98-107 pii 10.1016/j.jconrel.2016.11.011

Abstract

For nearly a century, aluminum salts have been the most widely used vaccine adjuvant formulation, and have thus established a history of safety and efficacy. Nevertheless, for extremely challenging disease targets such as tuberculosis or HIV, the adjuvant activity of aluminum salts may not be potent enough to achieve protective efficacy. Adsorption of TLR ligands to aluminum salts facilitates enhanced adjuvant activity, such as in the human papilloma virus vaccine Cervarix®. However, some TLR ligands such as TLR7/8 agonist imidazoquinolines do not efficiently adsorb to aluminum salts. The present report describes a formulation approach to solving this challenge by developing a lipid-based nanosuspension of a synthetic TLR7/8 ligand (3M-052) that facilitates adsorption to aluminum oxyhydroxide via the structural properties of the helper lipid employed. In immunized mice, the aluminum oxyhydroxide-adsorbed formulation of 3M-052 enhanced antibody and TH1-type cellular immune responses to vaccine antigens for tuberculosis and HIV.

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