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• W2051890667 endingPage "889" @default.
• W2051890667 startingPage "879" @default.
• W2051890667 abstract "Activity of adjuvanted vaccines is difficult to predict in vitro and in vivo. The wide compositional and conformational range of formulated adjuvants, from aluminum salts to oil-in-water emulsions, makes comparisons between physicochemical and immunological properties difficult. Even within a formulated adjuvant class, excipient selection and concentration can alter potency and physicochemical properties of the mixture. Complete characterization of physicochemical properties of adjuvanted vaccine formulations and relationship to biological response is necessary to move beyond a guess-and-check paradigm toward directed development. Here we present a careful physicochemical characterization of a two-component nanosuspension containing synthetic TLR-4 agonist glucopyranosyl lipid adjuvant (GLA) and 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) at various molar ratios. Physicochemical properties were compared with potency, as measured by stimulation of cytokine production in human whole blood. We found a surprising, nonlinear relationship between physicochemical properties and GLA–DPPC ratios that corresponded well with changes in biological activity. We discuss these data in light of the current understanding of TLR4 activation and the conformation–potency relationship in development of adjuvanted vaccines." @default.
• W2051890667 created "2016-06-24" @default.
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• W2051890667 date "2014-03-01" @default.
• W2051890667 modified "2023-10-17" @default.
• W2051890667 title "Modulating Potency: Physicochemical Characteristics are a Determining Factor of TLR4-Agonist Nanosuspension Activity" @default.
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• W2051890667 doi "https://doi.org/10.1002/jps.23868" @default.
• W2051890667 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24464844" @default.
• W2051890667 hasPublicationYear "2014" @default.
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