title: Adsorption of a synthetic TLR7/8 ligand to aluminum oxyhydroxide for enhanced vaccine adjuvant activity: A formulation approach.
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.
authors.affiliation: IDRI, 1616 Eastlake Ave, Seattle, WA 98102, USA; Dept of Global Health, University of Washington, Seattle, WA 98104, USA. Electronic address: cfox@idri.org.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Fox
authors.affiliation: IDRI, 1616 Eastlake Ave, Seattle, WA 98102, USA; Dept of Global Health, University of Washington, Seattle, WA 98104, USA.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Orr
authors.affiliation: IDRI, 1616 Eastlake Ave, Seattle, WA 98102, USA.
authors.forename: Neal
authors.initials: N
authors.lastname: Van Hoeven
authors.affiliation: IDRI, 1616 Eastlake Ave, Seattle, WA 98102, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Parker
authors.affiliation: IDRI, 1616 Eastlake Ave, Seattle, WA 98102, USA.
authors.forename: Traci J T
authors.initials: TJ
authors.lastname: Mikasa
authors.affiliation: IDRI, 1616 Eastlake Ave, Seattle, WA 98102, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Phan
authors.affiliation: IDRI, 1616 Eastlake Ave, Seattle, WA 98102, USA.
authors.forename: Elyse A
authors.initials: EA
authors.lastname: Beebe
authors.affiliation: IDRI, 1616 Eastlake Ave, Seattle, WA 98102, USA.
authors.forename: Ghislain I
authors.initials: GI
authors.lastname: Nana
authors.affiliation: IDRI, 1616 Eastlake Ave, Seattle, WA 98102, USA.
authors.forename: Sharvari W
authors.initials: SW
authors.lastname: Joshi
authors.affiliation: 3M Drug Delivery Systems, 3M Center, 275-3E-10, St. Paul, MN 55144, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Tomai
authors.affiliation: 3M Drug Delivery Systems, 3M Center, 275-3E-10, St. Paul, MN 55144, USA.
authors.forename: James
authors.initials: J
authors.lastname: Elvecrog
authors.affiliation: Profectus Biosciences, Inc., Baltimore, MD 21224, USA.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Fouts
authors.affiliation: IDRI, 1616 Eastlake Ave, Seattle, WA 98102, USA; Dept of Global Health, University of Washington, Seattle, WA 98104, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000327:Adsorption; D000536:Aluminum Hydroxide / Q000737:chemistry*; D000537:Aluminum Oxide / Q000737:chemistry*; D000818:Animals; D004355:Drug Stability; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000276:immunology; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D008024:Ligands; D008055:Lipids / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011804:Quinolines / Q000737:chemistry* / Q000276:immunology; D013499:Surface Properties; D051199:Toll-Like Receptor 7 / Q000378:metabolism*; D051200:Toll-Like Receptor 8 / Q000378:metabolism*; D032581:Tuberculosis Vaccines / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D007093:Imidazoles; D008024:Ligands; D008055:Lipids; D011804:Quinolines; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D032581:Tuberculosis Vaccines; D000536:Aluminum Hydroxide; C069471:aluminum oxide hydroxide; D000537:Aluminum Oxide