Hafner AM Corthésy B Merkle HP 2013 Current research and development of antigens for vaccination often center on purified recombinant proteins, viral subunits, synthetic oligopeptides or oligosaccharides, most of them suffering from being poorly immunogenic and subject to degradation. Hence, they call for efficient delivery systems and potent immunostimulants, jointly denoted as adjuvants. Particulate delivery systems like emulsions, liposomes, nanoparticles and microspheres may provide protection from degradation and facilitate the co-formulation of both the antigen and the immunostimulant. Synthetic double-stranded (ds) RNA, such as polyriboinosinic acid-polyribocytidylic acid, poly(I:C), is a mimic of viral dsRNA and, as such, a promising immunostimulant candidate for vaccines directed against intracellular pathogens. Poly(I:C) signaling is primarily dependent on Toll-like receptor 3 (TLR3), and on melanoma differentiation-associated gene-5 (MDA-5), and strongly drives cell-mediated immunity and a potent type I interferon response. However, stability and toxicity issues so far prevented the clinical application of dsRNAs as they undergo rapid enzymatic degradation and bear the potential to trigger undue immune stimulation as well as autoimmune disorders. This review addresses these concerns and suggests strategies to improve the safety and efficacy of immunostimulatory dsRNA formulations. The focus is on technological means required to lower the necessary dosage of poly(I:C), to target surface-modified microspheres passively or actively to antigen-presenting cells (APCs), to control their interaction with non-professional phagocytes and to modulate the resulting cytokine secretion profile. https://sonar.ch/global/documents/183978 eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.addr.2013.05.013 info:eu-repo/semantics/altIdentifier/pmid/23751781 Advanced drug delivery reviews. - 2013 AIM 2 APC Ampligen Autoimmunity BMDC C-type lectin receptor CLR CTAB CTL DAI DAMP DC DDA DEAE DNA-dependent activator of IFN-regulatory factor Dendritic cells Efficacy GM-CSF HFF IFN IFN-regulatory factor 3 IFN-γ-inducible protein 10 (CXCL10) IL IP 10 IRF 3 Immunostimulation LCs LPS Langerhans cells M720 MDA-5 MHC Microspheres MoDC Montanide ISA 720 NAP 1 NLR NOD-like receptor Non-professional phagocytes ODN OVA PAMP PEG PEI PK3 PLGA PLL PLL-g-PEG PRR PS Poly(l-lysine)-graft-poly(ethylene glycol) RIG I RLRs SLN Safety Surface modification T cell receptor TCR TDB TLR TLR3 ligands TNF-α Toll-like receptor Vaccine formulations absent-in-melanoma 2 antigen-presenting cell bone marrow-derived DC cetytrimethylammonium bromide cytotoxic T lymphocyte danger-associated molecular pattern dendritic cell diethylaminoethyl dimethyldioctadecylammonium double-stranded ds granulocyte macrophage colony-stimulating factor human foreskin fibroblast iDCs immature DCs interferon interleukin lipopolysaccharide mDC macrophage-inducible C type lectin major histocompatibility complex mature DC melanoma differentiation-associated gene—5 mincle monocyte-derived dendritic cell neutrophil activating peptide 1 oligodeoxynucleotide ovalbumin pDC pH-sensitive polyketal copolymer pathogen recognition receptor pathogen-associated molecular pattern plasmacytoid dendritic cell poly(A:U) poly(I:C) poly(I:C) stabilized with poly(l-lysine) and carboxymethylcellulose poly(I:C12U) poly(IC·LC) poly(ethylene glycol) poly(l-lysine) poly(lactic-co-glycolic acid) polyethyleneimine polyriboadenylic–polyribouridylic acid polyriboinosinic acid–polyribocytidylic acid polystyrene retinoic acid-inducible gene-I retinoic acid-inducible gene-I-like receptors solid-lipid nanoparticle trehalose 6,6′-dibehenate tumor necrosis factor-alpha Adjuvants, Immunologic Animals Antigens Dendritic Cells Humans Microspheres Poly I-C Toll-Like Receptor 3 Vaccines Particulate formulations for the delivery of poly(I:C) as vaccine adjuvant. http://purl.org/coar/resource_type/c_6501