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- W78584312 abstract "Abstract Inflammasome activation requires signaling of both the Toll-like receptor (TLR) and NLRP3 in antigen-presenting cells. We present a class of nanomaterials endowed with these two signals for rapid optimization of vaccine design. We constructed this system using an approach that incorporates lipopolysaccharides (LPS) onto the surface of nanoparticles constructed from a biocompatible polyester loaded with antigen. We demonstrate that LPS-modified particles, elicits potent humoral and cellular immunity against a model antigen, ovalbumin. Wild type macrophages pulsed with LPS-modified nanoparticles resulted in production of the proinflammatory cytokine IL-1β consistent with inflammasome activation. In comparison, NLRP3-deficient and caspase-1-deficient macrophages showed negligible production of IL-1β. Furthermore, when endocytosis and lysosomal destabilization were inhibited, inflammasome activity was diminished, supporting the notion that nanoparticles rupture lysosomal compartments and behave as 'danger signals'. The generality of this vaccination approach is tested by encapsulation of a recombinant West Nile envelope protein and demonstrated by protection against a murine model of West Nile encephalitis. The design of such an antigen delivery mechanism with the ability to stimulate two potent innate immune pathways represents a new approach to simultaneous antigen and adjuvant delivery." @default.
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- W78584312 date "2009-04-01" @default.
- W78584312 modified "2023-09-24" @default.
- W78584312 title "Inflammasome-activating biodegradable nanoparticulates as vaccine delivery systems (135.80)" @default.
- W78584312 doi "https://doi.org/10.4049/jimmunol.182.supp.135.80" @default.
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