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J Control Release. 2016 Dec 28;244(Pt A):98-107. doi: 10.1016/j.jconrel.2016.11.011. Epub 2016 Nov 12.

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

Author information

1
IDRI, 1616 Eastlake Ave, Seattle, WA 98102, USA; Dept of Global Health, University of Washington, Seattle, WA 98104, USA. Electronic address: cfox@idri.org.
2
IDRI, 1616 Eastlake Ave, Seattle, WA 98102, USA; Dept of Global Health, University of Washington, Seattle, WA 98104, USA.
3
IDRI, 1616 Eastlake Ave, Seattle, WA 98102, USA.
4
3M Drug Delivery Systems, 3M Center, 275-3E-10, St. Paul, MN 55144, USA.
5
Profectus Biosciences, Inc., Baltimore, MD 21224, USA.

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.

PMID:
27847326
PMCID:
PMC5176129
DOI:
10.1016/j.jconrel.2016.11.011
[Indexed for MEDLINE]
Free PMC Article

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