Combinatorial Delivery of Dual and Triple TLR Agonists via Polymeric Pathogen-like Particles Synergistically Enhances Innate and Adaptive Immune Responses.

ABSTRACT: Despite decades of research very few vaccine-adjuvants have received FDA approval. Two fundamental challenges plague clinical translation of vaccine-adjuvants: reducing acute toxicities that result from systemic diffusion of many soluble adjuvants, and delivering multiple adjuvants at the same time to mimic the synergistic immune-stimulation of pathogens, while being safe. In order to address these barriers, we evaluated combinations of four clinically relevant immune-agonists, specifically Toll-like receptor (TLR) ligands, using biodegradable, polymer microparticles. We tested them alone and in combinations of 2 or 3, for a total of 10 unique conditions. We evaluated primary bone-marrow-derived Dendritic Cell phenotypes and functionality, and identified several synergistic combinations. W

SUBMITTER: Madan-Lala R 

PROVIDER: S-EPMC5451393 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature