Self-Assembly of Immune Signals Improves Codelivery to Antigen Presenting Cells and Accelerates Signal Internalization, Processing Kinetics, and Immune Activation

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Michelle L BookstaverChristopher M Jewell

Abstract

Vaccines and immunotherapies that elicit specific types of immune responses offer transformative potential to tackle disease. The mechanisms governing the processing of immune signals-events that determine the type of response generated-are incredibly complex. Understanding these processes would inform more rational vaccine design by linking carrier properties, processing mechanisms, and relevant timescales to specific impacts on immune response. This goal is pursued using nanostructured materials-termed immune polyelectrolyte multilayers-built entirely from antigens and stimulatory toll-like receptors agonists (TLRas). This simplicity allows isolation and quantification of the rates and mechanisms of intracellular signal processing, and the link to activation of distinct immune pathways. Each vaccine component is internalized in a colocalized manner through energy-dependent caveolae-mediated endocytosis. This process results in trafficking through endosome/lysosome pathways and stimulation of TLRs expressed on endosomes/lysosomes. The maximum rates for these events occur within 4 h, but are detectable in minutes, ultimately driving downstream proimmune functions. Interestingly, these uptake, processing, and activation kinetics...Continue Reading

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Citations

Jan 4, 2019·Advanced Healthcare Materials·Joshua M Gammon, Christopher M Jewell
Nov 30, 2019·Advanced Materials·Haleigh B Eppler, Christopher M Jewell
Jul 10, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Yongjuan ZouGuanghui Ma
Jun 30, 2019·Advanced Materials·C Wyatt ShieldsSamir Mitragotri
Jan 29, 2020·Bioengineering & Translational Medicine·Krystina L Hess, Christopher M Jewell
Jan 26, 2021·Frontiers in Immunology·Shannon J TsaiChristopher M Jewell
May 24, 2021·Advanced Drug Delivery Reviews·Neha KapateSamir Mitragotri
Oct 20, 2020·Accounts of Chemical Research·Eugene FroimchukChristopher M Jewell

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