Particulate formulations for the delivery of poly(I:C) as vaccine adjuvant

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 an...

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Bibliographic Details
Published in	Advanced drug delivery reviews Vol. 65; no. 10; pp. 1386 - 1399
Main Authors	Hafner, Annina M., Corthésy, Blaise, Merkle, Hans P.
Format	Journal Article
Language	English
Published	Netherlands Elsevier B.V 01.10.2013
Subjects	Adjuvants, Immunologic - administration & dosage Adjuvants, Immunologic - chemistry Animals Antigens - administration & dosage Antigens - chemistry Autoimmunity Dendritic cells Dendritic Cells - immunology Efficacy Humans Immunostimulation Microspheres Non-professional phagocytes Poly I-C - administration & dosage Poly I-C - chemistry Safety Surface modification TLR3 ligands Toll-Like Receptor 3 - immunology Vaccine formulations Vaccines - administration & dosage Vaccines - chemistry Autoimmunity PS poly(I:C12U) CLR Non-professional phagocytes HFF MHC ds IP 10 PRR Microspheres SLN BMDC GM-CSF Vaccine formulations ODN PK3 IL Immunostimulation NAP 1 poly(A:U) mDC poly(IC·LC) IRF 3 OVA RIG I RLRs DDA AIM 2 TCR CTAB LPS IFN PLL TDB NLR TLR TLR3 ligands Safety LCs Surface modification Dendritic cells MoDC Efficacy M720 DAI MDA-5 pDC PLL-g-PEG mincle PAMP PLGA PEG APC TNF-α PEI poly(I:C) CTL DEAE iDCs DAMP DC neutrophil activating peptide 1 Montanide ISA 720 trehalose 6,6′-dibehenate major histocompatibility complex pH-sensitive polyketal copolymer tumor necrosis factor-alpha cetytrimethylammonium bromide Toll-like receptor bone marrow-derived DC T cell receptor solid-lipid nanoparticle dimethyldioctadecylammonium Langerhans cells immature DCs lipopolysaccharide dendritic cell polyriboinosinic acid–polyribocytidylic acid polyriboadenylic–polyribouridylic acid retinoic acid-inducible gene-I plasmacytoid dendritic cell monocyte-derived dendritic cell polystyrene double-stranded diethylaminoethyl mature DC poly(lactic-co-glycolic acid) poly(I:C) stabilized with poly(l-lysine) and carboxymethylcellulose melanoma differentiation-associated gene—5 poly(ethylene glycol) ovalbumin C-type lectin receptor oligodeoxynucleotide granulocyte macrophage colony-stimulating factor IFN-γ-inducible protein 10 (CXCL10) absent-in-melanoma 2 cytotoxic T lymphocyte human foreskin fibroblast Poly(l-lysine)-graft-poly(ethylene glycol) polyethyleneimine pathogen recognition receptor DNA-dependent activator of IFN-regulatory factor antigen-presenting cell interleukin pathogen-associated molecular pattern NOD-like receptor poly(l-lysine) IFN-regulatory factor 3 interferon danger-associated molecular pattern retinoic acid-inducible gene-I-like receptors Ampligen macrophage-inducible C type lectin
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ISSN	0169-409X 1872-8294 1872-8294
DOI	10.1016/j.addr.2013.05.013

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Abstract	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. [Display omitted]
AbstractList	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. 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.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. 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. [Display omitted]
Author	Corthésy, Blaise Hafner, Annina M. Merkle, Hans P.
Author_xml	– sequence: 1 givenname: Annina M. surname: Hafner fullname: Hafner, Annina M. organization: ETH Zurich, Institute of Pharmaceutical Sciences, CH-8093 Zurich, Switzerland – sequence: 2 givenname: Blaise surname: Corthésy fullname: Corthésy, Blaise organization: CHUV, Division of Immunology and Allergy, CH-1005 Lausanne, Switzerland – sequence: 3 givenname: Hans P. surname: Merkle fullname: Merkle, Hans P. email: hmerkle@pharma.ethz.ch organization: ETH Zurich, Institute of Pharmaceutical Sciences, CH-8093 Zurich, Switzerland
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/23751781$$D View this record in MEDLINE/PubMed
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Keywords	Autoimmunity PS poly(I:C12U) CLR Non-professional phagocytes HFF MHC ds IP 10 PRR Microspheres SLN BMDC GM-CSF Vaccine formulations ODN PK3 IL Immunostimulation NAP 1 poly(A:U) mDC poly(IC·LC) IRF 3 OVA RIG I RLRs DDA AIM 2 TCR CTAB LPS IFN PLL TDB NLR TLR TLR3 ligands Safety LCs Surface modification Dendritic cells MoDC Efficacy M720 DAI MDA-5 pDC PLL-g-PEG mincle PAMP PLGA PEG APC TNF-α PEI poly(I:C) CTL DEAE iDCs DAMP DC neutrophil activating peptide 1 Montanide ISA 720 trehalose 6,6′-dibehenate major histocompatibility complex pH-sensitive polyketal copolymer tumor necrosis factor-alpha cetytrimethylammonium bromide Toll-like receptor bone marrow-derived DC T cell receptor solid-lipid nanoparticle dimethyldioctadecylammonium Langerhans cells immature DCs lipopolysaccharide dendritic cell polyriboinosinic acid–polyribocytidylic acid polyriboadenylic–polyribouridylic acid retinoic acid-inducible gene-I plasmacytoid dendritic cell monocyte-derived dendritic cell polystyrene double-stranded diethylaminoethyl mature DC poly(lactic-co-glycolic acid) poly(I:C) stabilized with poly(l-lysine) and carboxymethylcellulose melanoma differentiation-associated gene—5 poly(ethylene glycol) ovalbumin C-type lectin receptor oligodeoxynucleotide granulocyte macrophage colony-stimulating factor IFN-γ-inducible protein 10 (CXCL10) absent-in-melanoma 2 cytotoxic T lymphocyte human foreskin fibroblast Poly(l-lysine)-graft-poly(ethylene glycol) polyethyleneimine pathogen recognition receptor DNA-dependent activator of IFN-regulatory factor antigen-presenting cell interleukin pathogen-associated molecular pattern NOD-like receptor poly(l-lysine) IFN-regulatory factor 3 interferon danger-associated molecular pattern retinoic acid-inducible gene-I-like receptors Ampligen macrophage-inducible C type lectin
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Snippet	Current research and development of antigens for vaccination often center on purified recombinant proteins, viral subunits, synthetic oligopeptides or...
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SubjectTerms	Adjuvants, Immunologic - administration & dosage Adjuvants, Immunologic - chemistry Animals Antigens - administration & dosage Antigens - chemistry Autoimmunity Dendritic cells Dendritic Cells - immunology Efficacy Humans Immunostimulation Microspheres Non-professional phagocytes Poly I-C - administration & dosage Poly I-C - chemistry Safety Surface modification TLR3 ligands Toll-Like Receptor 3 - immunology Vaccine formulations Vaccines - administration & dosage Vaccines - chemistry
Title	Particulate formulations for the delivery of poly(I:C) as vaccine adjuvant
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