Vaccine adjuvant uses of poly-IC and derivatives

References

• Coffman RL , Sher A , Seder RA . Vaccine adjuvants: putting innate immunity to work. Immunity 2010;33:492-503
   PubMed Web of Science ®Google Scholar
• Steinhagen F , Kinjo T , Bode C , et al. TLR-based immune adjuvants. Vaccine 2011;29:3341-55
   PubMed Web of Science ®Google Scholar
• Pulendran B , Ahmed R . Immunological mechanisms of vaccination. Nat Immunol 2011;12:509-17
   PubMed Web of Science ®Google Scholar
• Schijns VE , Lavelle EC . Trends in vaccine adjuvants. Expert Rev Vaccines 2011;10:539-50
   PubMed Web of Science ®Google Scholar
• Hafner AM , Corthesy B , Merkle HP . Particulate formulations for the delivery of poly(I:C) as vaccine adjuvant. Adv Drug Deliv Rev 2013;65:1386-99
   PubMed Web of Science ®Google Scholar
• Reed SG , Orr MT , Fox CB . Key roles of adjuvants in modern vaccines. Nat Med 2013;19:1597-608
   PubMed Web of Science ®Google Scholar
• Lambrecht BN , Kool M , Willart MA , et al. Mechanism of action of clinically approved adjuvants. Curr Opin Immunol 2009;21:23-9
   PubMed Web of Science ®Google Scholar
• Li H , Nookala S , Re F . Aluminum hydroxide adjuvants activate caspase-1 and induce IL-1beta and IL-18 release. J Immunol 2007;178:5271-6
   PubMed Web of Science ®Google Scholar
• Oleszycka E , Lavelle EC . Immunomodulatory properties of the vaccine adjuvant alum. Curr Opin Immunol 2014;28C:1-5
   Web of Science ®Google Scholar
• Brunner R , Jensen-Jarolim E , Pali-Scholl I . The ABC of clinical and experimental adjuvants–a brief overview. Immunol Lett 2010;128:29-35
   PubMed Web of Science ®Google Scholar
• Bode C , Zhao G , Steinhagen F , et al. CpG DNA as a vaccine adjuvant. Expert Rev Vaccines 2011;10:499-511
   PubMed Web of Science ®Google Scholar
• Mbow ML , De Gregorio E , Valiante NM , et al. New adjuvants for human vaccines. Curr Opin Immunol 2010;22:411-16
   PubMed Web of Science ®Google Scholar
• Caskey M , Lefebvre F , Filali-Mouhim A , et al. Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans. J Exp Med 2011;208:2357-66
   PubMed Web of Science ®Google Scholar
• Chew V , Tow C , Huang C , et al. Toll-like receptor 3 expressing tumor parenchyma and infiltrating natural killer cells in hepatocellular carcinoma patients. J Natl Cancer Inst 2012;104:1796-807
   PubMedGoogle Scholar
• Longhi MP , Trumpfheller C , Idoyaga J , et al. Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. J Exp Med 2009;206:1589-602
   PubMed Web of Science ®Google Scholar
• Flynn BJ , Kastenmuller K , Wille-Reece U , et al. Immunization with HIV Gag targeted to dendritic cells followed by recombinant New York vaccinia virus induces robust T-cell immunity in nonhuman primates. Proc Natl Acad Sci USA 2011;108:7131-6
   PubMed Web of Science ®Google Scholar
• Nagato T , Lee YR , Harabuchi Y , et al. Combinatorial immunotherapy of polyinosinic-polycytidylic acid and blockade of programmed death-ligand 1 induce effective CD8 T-cell responses against established tumors. Clin Cancer Res 2014;20:1223-34
   PubMed Web of Science ®Google Scholar
• Wick DA , Webb JR . A novel, broad spectrum therapeutic HPV vaccine targeting the E7 proteins of HPV16, 18, 31, 45 and 52 that elicits potent E7-specific CD8T cell immunity and regression of large, established, E7-expressing TC-1 tumors. Vaccine 2011;29:7857-66
   PubMed Web of Science ®Google Scholar
• Zhu X , Fallert-Junecko BA , Fujita M , et al. Poly-ICLC promotes the infiltration of effector T cells into intracranial gliomas via induction of CXCL10 in IFN-alpha and IFN-gamma dependent manners. Cancer Immunol Immunother 2010;59:1401-9
   PubMed Web of Science ®Google Scholar
• Zhu X , Nishimura F , Sasaki K , et al. Toll like receptor-3 ligand poly-ICLC promotes the efficacy of peripheral vaccinations with tumor antigen-derived peptide epitopes in murine CNS tumor models. J Transl Med 2007;5:10
   PubMed Web of Science ®Google Scholar
• Stahl-Hennig C , Eisenblatter M , Jasny E , et al. Synthetic double-stranded RNAs are adjuvants for the induction of T helper 1 and humoral immune responses to human papillomavirus in rhesus macaques. PLoS Pathog 2009;5:e1000373
   PubMed Web of Science ®Google Scholar
• Kajiwara K , Morishima H , Akiyama K , et al. Expression and function of the inducible costimulator ligand B7-H2 in human airway smooth muscle cells. Allergol Int 2009;58:573-83
   PubMedGoogle Scholar
• Wang Y , Cella M , Gilfillan S , et al. Cutting edge: polyinosinic:polycytidylic acid boosts the generation of memory CD8 T cells through melanoma differentiation-associated protein 5 expressed in stromal cells. J Immunol 2010;184:2751-5
   PubMed Web of Science ®Google Scholar
• Mitoma H , Hanabuchi S , Kim T , et al. The DHX33 RNA helicase senses cytosolic RNA and activates the NLRP3 inflammasome. Immunity 2013;39:123-35
   PubMed Web of Science ®Google Scholar
• Chattopadhyay S , Sen GC . dsRNA-Activation of TLR3 and RLR Signaling: gene Induction-Dependent and Independent Effects. J Interferon Cytokine Res 2014;34:427-36
   PubMed Web of Science ®Google Scholar
• Alexopoulou L , Holt AC , Medzhitov R , et al. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 2001;413:732-8
   PubMed Web of Science ®Google Scholar
• Kato H , Takeuchi O , Mikamo-Satoh E , et al. Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J Exp Med 2008;205:1601-10
   PubMed Web of Science ®Google Scholar
• Nemes MM , Tytell AA , Lampson GP , et al. Inducers of interferon and host resistance. VI. Antiviral efficacy of poly I:C in animal models. Proc Soc Exp Biol Med 1969;132:776-83
   PubMed Web of Science ®Google Scholar
• Schreiner B , Voss J , Wischhusen J , et al. Expression of toll-like receptors by human muscle cells in vitro and in vivo: TLR3 is highly expressed in inflammatory and HIV myopathies, mediates IL-8 release and up-regulation of NKG2D-ligands. FASEB J 2006;20:118-20
   PubMed Web of Science ®Google Scholar
• Cario E , Podolsky DK . Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun 2000;68:7010-17
   PubMed Web of Science ®Google Scholar
• Lech M , Avila-Ferrufino A , Skuginna V , et al. Quantitative expression of RIG-like helicase, NOD-like receptor and inflammasome-related mRNAs in humans and mice. Int Immunol 2010;22:717-28
   PubMed Web of Science ®Google Scholar
• Robinson RA , DeVita VT , Levy HB , et al. A phase I-II trial of multiple-dose polyriboinosic-polyribocytidylic acid in patieonts with leukemia or solid tumors. J Natl Cancer Inst 1976;57:599-602
   PubMedGoogle Scholar
• Carter WA , Pitha PM , Marshall LW , et al. Structural requirements of the rI n -rC n complex for induction of human interferon. J Mol Biol 1972;70:567-87
   PubMed Web of Science ®Google Scholar
• Do Y , Didierlaurent AM , Ryu S , et al. Induction of pulmonary mucosal immune responses with a protein vaccine targeted to the DEC-205/CD205 receptor. Vaccine 2012;30:6359-67
   PubMed Web of Science ®Google Scholar
• Cheong C , Choi JH , Vitale L , et al. Improved cellular and humoral immune responses in vivo following targeting of HIV Gag to dendritic cells within human anti-human DEC205 monoclonal antibody. Blood 2010;116:3828-38
   PubMed Web of Science ®Google Scholar
• Gowen BB , Wong MH , Jung KH , et al. TLR3 is essential for the induction of protective immunity against Punta Toro Virus infection by the double-stranded RNA (dsRNA), poly(I:C12U), but not Poly(I:C): differential recognition of synthetic dsRNA molecules. J Immunol 2007;178:5200-8
   PubMed Web of Science ®Google Scholar
• Ichinohe T , Kawaguchi A , Tamura S , et al. Intranasal immunization with H5N1 vaccine plus Poly I:poly C12U, a Toll-like receptor agonist, protects mice against homologous and heterologous virus challenge. Microbes Infect 2007;9:1333-40
   PubMed Web of Science ®Google Scholar
• Ichinohe T , Ainai A , Tashiro M , et al. PolyI:polyC12U adjuvant-combined intranasal vaccine protects mice against highly pathogenic H5N1 influenza virus variants. Vaccine 2009;27:6276-9
   PubMed Web of Science ®Google Scholar
• Avril T , de Tayrac M , Leberre C , et al. Not all polyriboinosinic-polyribocytidylic acids (Poly I:C) are equivalent for inducing maturation of dendritic cells: implication for alpha-type-1 polarized DCs. J Immunother 2009;32:353-62
   PubMed Web of Science ®Google Scholar
• Ma Y , Ross AC . Toll-like receptor 3 ligand and retinoic acid enhance germinal center formation and increase the tetanus toxoid vaccine response. Clin Vaccine Immunol 2009;16:1476-84
   PubMed Web of Science ®Google Scholar
• Hu F , Yu X , Wang H , et al. ER stress and its regulator X-box-binding protein-1 enhance polyIC-induced innate immune response in dendritic cells. Eur J Immunol 2011;41:1086-97
   PubMed Web of Science ®Google Scholar
• Gitlin L , Barchet W , Gilfillan S , et al. Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus. Proc Natl Acad Sci USA 2006;103:8459-64
   PubMed Web of Science ®Google Scholar
• Matsumoto M , Kikkawa S , Kohase M , et al. Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling. Biochem Biophys Res Commun 2002;293:1364-9
   PubMed Web of Science ®Google Scholar
• Kato H , Takeuchi O , Sato S , et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 2006;441:101-5
   PubMed Web of Science ®Google Scholar
• Le Bon A , Schiavoni G , D’Agostino G , et al. Type i interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo. Immunity 2001;14:461-70
   PubMed Web of Science ®Google Scholar
• Le Bon A , Thompson C , Kamphuis E , et al. Cutting edge: enhancement of antibody responses through direct stimulation of B and T cells by type I IFN. J Immunol 2006;176:2074-8
   PubMed Web of Science ®Google Scholar
• Zou J , Kawai T , Tsuchida T , et al. Poly IC triggers a cathepsin D- and IPS-1-dependent pathway to enhance cytokine production and mediate dendritic cell necroptosis. Immunity 2013;38:717-28
   PubMed Web of Science ®Google Scholar
• Lauterbach H , Bathke B , Gilles S , et al. Mouse CD8alpha+ DCs and human BDCA3+ DCs are major producers of IFN-lambda in response to poly IC. J Exp Med 2010;207:2703-17
   PubMed Web of Science ®Google Scholar
• Kelly A , Fahey R , Fletcher JM , et al. CD141(+) myeloid dendritic cells are enriched in healthy human liver. J Hepatol 2014;60:135-42
   PubMed Web of Science ®Google Scholar
• Ding Y , Wilkinson A , Idris A , et al. FLT3-ligand treatment of humanized mice results in the generation of large numbers of CD141+ and CD1c+ dendritic cells in vivo. J Immunol 2014;192:1982-9
   PubMed Web of Science ®Google Scholar
• Yamamoto M , Sato S , Hemmi H , et al. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 2003;301:640-3
   PubMed Web of Science ®Google Scholar
• Oshiumi H , Matsumoto M , Funami K , et al. TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction. Nat Immunol 2003;4:161-7
   PubMed Web of Science ®Google Scholar
• Swiecki M , Wang Y , Vermi W , et al. Type I interferon negatively controls plasmacytoid dendritic cell numbers in vivo. J Exp Med 2011;208:2367-74
   PubMed Web of Science ®Google Scholar
• Reimer T , Brcic M , Schweizer M , et al. poly(I:C) and LPS induce distinct IRF3 and NF-kappaB signaling during type-I IFN and TNF responses in human macrophages. J Leukoc Biol 2008;83:1249-57
   PubMed Web of Science ®Google Scholar
• Hochrein H , Shortman K , Vremec D , et al. Differential production of IL-12, IFN-alpha, and IFN-gamma by mouse dendritic cell subsets. J Immunol 2001;166:5448-55
   PubMed Web of Science ®Google Scholar
• Verdijk RM , Mutis T , Esendam B , et al. Polyriboinosinic polyribocytidylic acid (poly(I:C)) induces stable maturation of functionally active human dendritic cells. J Immunol 1999;163:57-61
   PubMed Web of Science ®Google Scholar
• Le Bon A , Etchart N , Rossmann C , et al. Cross-priming of CD8+ T cells stimulated by virus-induced type I interferon. Nat Immunol 2003;4:1009-15
   PubMed Web of Science ®Google Scholar
• Schulz O , Diebold SS , Chen M , et al. Toll-like receptor 3 promotes cross-priming to virus-infected cells. Nature 2005;433:887-92
   PubMed Web of Science ®Google Scholar
• Durand V , Wong SY , Tough DF , et al. IFN-alpha/beta-dependent cross-priming induced by specific toll-like receptor agonists. Vaccine 2006;24(Suppl 2):S2-22-3
   Google Scholar
• Marrack P , Kappler J , Mitchell T . Type I interferons keep activated T cells alive. J Exp Med 1999;189:521-30
   PubMed Web of Science ®Google Scholar
• Curtsinger JM , Valenzuela JO , Agarwal P , et al. Type I IFNs provide a third signal to CD8 T cells to stimulate clonal expansion and differentiation. J Immunol 2005;174:4465-9
   PubMed Web of Science ®Google Scholar
• Kolumam GA , Thomas S , Thompson LJ , et al. Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection. J Exp Med 2005;202:637-50
   PubMed Web of Science ®Google Scholar
• Havenar-Daughton C , Kolumam GA , Murali-Krishna K . Cutting Edge: the direct action of type I IFN on CD4 T cells is critical for sustaining clonal expansion in response to a viral but not a bacterial infection. J Immunol 2006;176:3315-19
   PubMed Web of Science ®Google Scholar
• Wiesel M , Kratky W , Oxenius A . Type I IFN substitutes for T cell help during viral infections. J Immunol 2011;186:754-63
   PubMed Web of Science ®Google Scholar
• Perret R , Sierro SR , Botelho NK , et al. Adjuvants that improve the ratio of antigen-specific effector to regulatory T cells enhance tumor immunity. Cancer Res 2013;73:6597-608
   PubMed Web of Science ®Google Scholar
• Ngoi SM , Tovey MG , Vella AT . Targeting poly(I:C) to the TLR3-independent pathway boosts effector CD8 T cell differentiation through IFN-alpha/beta. J Immunol 2008;181:7670-80
   PubMed Web of Science ®Google Scholar
• Gunthner R , Kumar VR , Lorenz G , et al. Pattern-recognition receptor signaling regulator mRNA expression in humans and mice, and in transient inflammation or progressive fibrosis. Int J Mol Sci 2013;14:18124-47
   PubMed Web of Science ®Google Scholar
• Seok J , Warren HS , Cuenca AG , et al. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci USA 2013;110:3507-12
   PubMed Web of Science ®Google Scholar
• Mestas J , Hughes CC . Of mice and not men: differences between mouse and human immunology. J Immunol 2004;172:2731-8
   PubMed Web of Science ®Google Scholar
• Rehli M . Of mice and men: species variations of Toll-like receptor expression. Trends Immunol 2002;23:375-8
   PubMed Web of Science ®Google Scholar
• Ferrero I , Held W , Wilson A , et al. Mouse CD11c(+) B220(+) Gr1(+) plasmacytoid dendritic cells develop independently of the T-cell lineage. Blood 2002;100:2852-7
   PubMed Web of Science ®Google Scholar
• Jongbloed SL , Kassianos AJ , McDonald KJ , et al. Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens. J Exp Med 2010;207:1247-60
   PubMed Web of Science ®Google Scholar
• Muzio M , Bosisio D , Polentarutti N , et al. Differential expression and regulation of toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. J Immunol 2000;164:5998-6004
   PubMed Web of Science ®Google Scholar
• Kadowaki N , Ho S , Antonenko S , et al. Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J Exp Med 2001;194:863-9
   PubMed Web of Science ®Google Scholar
• Heinz S , Haehnel V , Karaghiosoff M , et al. Species-specific regulation of Toll-like receptor 3 genes in men and mice. J Biol Chem 2003;278:21502-9
   PubMed Web of Science ®Google Scholar
• Lundberg AM , Drexler SK , Monaco C , et al. Key differences in TLR3/poly I:C signaling and cytokine induction by human primary cells: a phenomenon absent from murine cell systems. Blood 2007;110:3245-52
   PubMed Web of Science ®Google Scholar
• Mian MF , Ahmed AN , Rad M , et al. Length of dsRNA (poly I:C) drives distinct innate immune responses, depending on the cell type. J Leukoc Biol 2013;94:1025-36
   PubMed Web of Science ®Google Scholar
• Trumpfheller C , Caskey M , Nchinda G , et al. The microbial mimic poly IC induces durable and protective CD4+ T cell immunity together with a dendritic cell targeted vaccine. Proc Natl Acad Sci USA 2008;105:2574-9
   PubMed Web of Science ®Google Scholar
• Engel AL , Holt GE , Lu H . The pharmacokinetics of Toll-like receptor agonists and the impact on the immune system. Expert Rev Clin Pharmacol 2011;4:275-89
   PubMedGoogle Scholar
• Brodsky I , Strayer DR , Krueger LJ , et al. Clinical studies with ampligen (mismatched double-stranded RNA). J Biol Response Mod 1985;4:669-75
   PubMedGoogle Scholar
• Hearl WG , Johnston MI . A misaligned double-stranded RNA, poly(I).poly(C12,U), induces accumulation of 2’,5’-oligoadenylates in mouse tissues. Biochem Biophys Res Commun 1986;138:40-6
   PubMed Web of Science ®Google Scholar
• Adams M , Navabi H , Jasani B , et al. Dendritic cell (DC) based therapy for cervical cancer: use of DC pulsed with tumour lysate and matured with a novel synthetic clinically non-toxic double stranded RNA analogue poly [I]:poly [C(12)U] (Ampligen R). Vaccine 2003;21:787-90
   PubMed Web of Science ®Google Scholar
• Navabi H , Jasani B , Reece A , et al. A clinical grade poly I:C-analogue (Ampligen) promotes optimal DC maturation and Th1-type T cell responses of healthy donors and cancer patients in vitro. Vaccine 2009;27:107-15
   PubMed Web of Science ®Google Scholar
• Welters MJ , Bijker MS , van den Eeden SJ , et al. Multiple CD4 and CD8 T-cell activation parameters predict vaccine efficacy in vivo mediated by individual DC-activating agonists. Vaccine 2007;25:1379-89
   PubMed Web of Science ®Google Scholar
• Levy HB , Baer G , Baron S , et al. A modified polyriboinosinic-polyribocytidylic acid complex that induces interferon in primates. J Infect Dis 1975;132:434-9
   PubMed Web of Science ®Google Scholar
• Sammons ML , Stephen EL , Levy HB , et al. Interferon induction in cynomolgus and rhesus monkey after repeated doses of a modified polyriboinosinic-polyribocytidylic acid complex. Antimicrob Agents Chemother 1977;11:80-3
   PubMed Web of Science ®Google Scholar
• Martins KA , Steffens JT , van Tongeren SA , et al. Toll-like receptor agonist augments virus-like particle-mediated protection from ebola virus with transient immune activation. PLoS One 2014;9:e89735
   PubMed Web of Science ®Google Scholar
• Calzascia T , Masson F , Di Berardino-Besson W , et al. Homing phenotypes of tumor-specific CD8 T cells are predetermined at the tumor site by crosspresenting APCs. Immunity 2005;22:175-84
   PubMed Web of Science ®Google Scholar
• Zhu X , Fujita M , Snyder LA , et al. Systemic delivery of neutralizing antibody targeting CCL2 for glioma therapy. J Neurooncol 2011;104:83-92
   PubMed Web of Science ®Google Scholar
• Couzin-Frankel J . Breakthrough of the year 2013. Cancer immunotherapy. Science 2013;342:1432-3
   PubMed Web of Science ®Google Scholar
• Butt AQ , Mills KH . Immunosuppressive networks and checkpoints controlling antitumor immunity and their blockade in the development of cancer immunotherapeutics and vaccines. Oncogene 2013. [Epub ahead of print]
   Web of Science ®Google Scholar
• Gelao L , Criscitiello C , Esposito A , et al. Immune checkpoint blockade in cancer treatment: a double-edged sword cross-targeting the host as an “innocent bystander”. Toxins (Basel) 2014;6:914-33
   PubMed Web of Science ®Google Scholar
• Park H , Adamson L , Ha T , et al. Polyinosinic-Polycytidylic Acid Is the Most Effective TLR Adjuvant for SIV Gag Protein-Induced T Cell Responses In Nonhuman Primates. J Immunol 2013;190:4103-15
   PubMed Web of Science ®Google Scholar
• Houston WE , Crabbs CL , Stephen EL , et al. Modified polyriboinosinic-polyribocytidylic acid, an immunological adjuvant. Infect Immun 1976;14:318-19
   PubMed Web of Science ®Google Scholar
• Stephen EL , Hilmas DE , Mangiafico JA , et al. Swine influenza virus vaccine: potentiation of antibody responses in rhesus monkeys. Science 1977;197:1289-90
   PubMed Web of Science ®Google Scholar
• Ichinohe T , Ainai A , Ami Y , et al. Intranasal administration of adjuvant-combined vaccine protects monkeys from challenge with the highly pathogenic influenza A H5N1 virus. J Med Virol 2010;82:1754-61
   PubMed Web of Science ®Google Scholar
• Tewari K , Flynn BJ , Boscardin SB , et al. Poly(I:C) is an effective adjuvant for antibody and multi-functional CD4+ T cell responses to Plasmodium falciparum circumsporozoite protein (CSP) and alphaDEC-CSP in non human primates. Vaccine 2010;28:7256-66
   PubMed Web of Science ®Google Scholar
• Kastenmuller K , Espinosa DA , Trager L , et al. Full-length P. falciparum circumsporozoite protein administered with poly-ICLC or GLA/SE elicits potent antibody and CD4+ T cell immunity and protection in mice. Infect Immun 2012;81(3):789-800
   PubMed Web of Science ®Google Scholar
• Cho HI , Celis E . Optimized peptide vaccines eliciting extensive CD8 T-cell responses with therapeutic antitumor effects. Cancer Res 2009;69:9012-19
   PubMed Web of Science ®Google Scholar
• Ohlfest JR , Andersen BM , Litterman AJ , et al. Vaccine injection site matters: qualitative and quantitative defects in CD8 T cells primed as a function of proximity to the tumor in a murine glioma model. J Immunol 2013;190:613-20
   PubMed Web of Science ®Google Scholar
• Thompson KA , Strayer DR , Salvato PD , et al. Results of a double-blind placebo-controlled study of the double-stranded RNA drug polyI:polyC12U in the treatment of HIV infection. Eur J Clin Microbiol Infect Dis 1996;15:580-7
   PubMed Web of Science ®Google Scholar
• Carter WA , Ventura D , Shapiro DE , et al. Mismatched double-stranded RNA, Ampligen (poly(I): poly(C12U), demonstrates antiviral and immunostimulatory activities in HIV disease. Int J Immunopharmacol 1991;13 Suppl 1:69-76
   PubMed Web of Science ®Google Scholar
• Mitchell WM , Montefiori DC , Robinson WE Jr , et al. Mismatched double-stranded RNA (ampligen) reduces concentration of zidovudine (azidothymidine) required for in-vitro inhibition of human immunodeficiency virus. Lancet 1987;1:890-2
   PubMed Web of Science ®Google Scholar
• Montefiori DC , Pellegrino MG , Robinson WE Jr , et al. Inhibition of HIV-1 proviral DNA synthesis and RNA accumulation by mismatched dsRNA. Biochem Biophys Res Commun 1989;158:943-50
   PubMed Web of Science ®Google Scholar
• Montefiori DC , Robinson WE Jr , Mitchell WM . Mismatched dsRNA (ampligen) induces protection against genomic variants of the human immunodeficiency virus type 1 (HIV-1) in a multiplicity of target cells. Antiviral Res 1988;9:47-55
   PubMed Web of Science ®Google Scholar
• Strayer DR , Carter WA , Brodsky I , et al. A controlled clinical trial with a specifically configured RNA drug, poly(I).poly(C12U), in chronic fatigue syndrome. Clin Infect Dis 1994;18(Suppl 1):S88-95
   PubMed Web of Science ®Google Scholar
• Suhadolnik RJ , Reichenbach NL , Hitzges P , et al. Changes in the 2-5A synthetase/RNase L antiviral pathway in a controlled clinical trial with poly(I)-poly(C12U) in chronic fatigue syndrome. In Vivo 1994;8:599-604
   PubMedGoogle Scholar
• Strayer DR , Carter WA , Stouch BC , et al. A double-blind, placebo-controlled, randomized, clinical trial of the TLR-3 agonist rintatolimod in severe cases of chronic fatigue syndrome. PLoS One 2012;7:e31334
   PubMed Web of Science ®Google Scholar
• Jasani B , Navabi H , Adams M . Ampligen: a potential toll-like 3 receptor adjuvant for immunotherapy of cancer. Vaccine 2009;27:3401-4
   PubMed Web of Science ®Google Scholar
• Lampkin BC , Levine AS , Levy H , et al. Phase II trial of poly(I,C)-LC, an interferon inducer, in the treatment of children with acute leukemia and neuroblastoma: a report from the Children’s Cancer Study Group. J Biol Response Mod 1985;4:531-7
   PubMedGoogle Scholar
• Stevenson HC , Abrams PG , Schoenberger CS , et al. A phase I evaluation of poly(I,C)-LC in cancer patients. J Biol Response Mod 1985;4:650-5
   PubMedGoogle Scholar
• Ewel CH , Urba WJ , Kopp WC , et al. Polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose in combination with interleukin 2 in patients with cancer: clinical and immunological effects. Cancer Res 1992;52:3005-10
   PubMed Web of Science ®Google Scholar
• Salazar AM , Levy HB , Ondra S , et al. Long-term treatment of malignant gliomas with intramuscularly administered polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose: an open pilot study. Neurosurgery 1996;38:1096-103; discussion 1103-1094
   PubMed Web of Science ®Google Scholar
• Butowski N , Lamborn KR , Lee BL , et al. A North American brain tumor consortium phase II study of poly-ICLC for adult patients with recurrent anaplastic gliomas. J Neurooncol 2009;91:183-9
   PubMed Web of Science ®Google Scholar
• Butowski N , Chang SM , Junck L , et al. A phase II clinical trial of poly-ICLC with radiation for adult patients with newly diagnosed supratentorial glioblastoma: a North American Brain Tumor Consortium (NABTC01-05). J Neurooncol 2009;91:175-82
   PubMed Web of Science ®Google Scholar
• Rosenfeld MR , Chamberlain MC , Grossman SA , et al. A multi-institution phase II study of poly-ICLC and radiotherapy with concurrent and adjuvant temozolomide in adults with newly diagnosed glioblastoma. Neuro Oncol 2010;12:1071-7
   PubMed Web of Science ®Google Scholar
• Hartman LL , Crawford JR , Makale MT , et al. Pediatric Phase II trials of poly-ICLC in the management of newly diagnosed and recurrent brain tumors. J Pediatr Hematol Oncol 2013;36(6):451-7
   Web of Science ®Google Scholar
• Okada H , Kalinski P , Ueda R , et al. Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma. J Clin Oncol 2011;29:330-6
   PubMed Web of Science ®Google Scholar
• Prins RM , Soto H , Konkankit V , et al. Gene expression profile correlates with T-cell infiltration and relative survival in glioblastoma patients vaccinated with dendritic cell immunotherapy. Clin Cancer Res 2011;17:1603-15
   PubMed Web of Science ®Google Scholar
• Sabbatini P , Tsuji T , Ferran L , et al. Phase I trial of overlapping long peptides from a tumor self-antigen and poly-ICLC shows rapid induction of integrated immune response in ovarian cancer patients. Clin Cancer Res 2012;18:6497-508
   PubMed Web of Science ®Google Scholar
• Rapoport AP , Aqui NA , Stadtmauer EA , et al. Combination immunotherapy after ASCT for multiple myeloma using MAGE-A3/Poly-ICLC immunizations followed by adoptive transfer of vaccine-primed and costimulated autologous T cells. Clin Cancer Res 2014;20:1355-65
   PubMed Web of Science ®Google Scholar
• Morse MA , Chapman R , Powderly J , et al. Phase I study utilizing a novel antigen-presenting cell-targeted vaccine with Toll-like receptor stimulation to induce immunity to self-antigens in cancer patients. Clin Cancer Res 2011;17:4844-53
   PubMed Web of Science ®Google Scholar
• Salazar AM , Erlich RB , Mark A , et al. Therapeutic in situ autovaccination against solid cancers with intratumoral Poly-ICLC: case report, hypothesis, and clinical trial. Cancer Immunol Res 2014;2:720-4
   PubMed Web of Science ®Google Scholar
• Garaude J , Kent A , van Rooijen N , et al. Simultaneous targeting of toll- and nod-like receptors induces effective tumor-specific immune responses. Sci Transl Med 2012;4; 120ra116
   PubMed Web of Science ®Google Scholar
• McNally B , Willette M , Ye F , et al. Intranasal administration of dsRNA analog poly(I:C) induces interferon-alpha receptor-dependent accumulation of antigen experienced T cells in the airways. PLoS One 2012;7:e51351
   PubMed Web of Science ®Google Scholar
• Perrot I , Deauvieau F , Massacrier C , et al. TLR3 and Rig-like receptor on myeloid dendritic cells and Rig-like receptor on human NK cells are both mandatory for production of IFN-gamma in response to double-stranded RNA. J Immunol 2010;185:2080-8
   PubMed Web of Science ®Google Scholar
• Lang KS , Recher M , Junt T , et al. Toll-like receptor engagement converts T-cell autoreactivity into overt autoimmune disease. Nat Med 2005;11:138-45
   PubMed Web of Science ®Google Scholar
• Weck MM , Grunebach F , Werth D , et al. TLR ligands differentially affect uptake and presentation of cellular antigens. Blood 2007;109:3890-4
   PubMed Web of Science ®Google Scholar
• Watts C , West MA , Zaru R. TL R signalling regulated antigen presentation in dendritic cells. Curr Opin Immunol 2010;22:124-30
   PubMed Web of Science ®Google Scholar
• Mouries J , Moron G , Schlecht G , et al. Plasmacytoid dendritic cells efficiently cross-prime naive T cells in vivo after TLR activation. Blood 2008;112:3713-22
   PubMed Web of Science ®Google Scholar
• Wilson NS , Behrens GM , Lundie RJ , et al. Systemic activation of dendritic cells by Toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity. Nat Immunol 2006;7:165-72
   PubMed Web of Science ®Google Scholar
• Young LJ , Wilson NS , Schnorrer P , et al. Dendritic cell preactivation impairs MHC class II presentation of vaccines and endogenous viral antigens. Proc Natl Acad Sci USA 2007;104:17753-8
   PubMed Web of Science ®Google Scholar
• Vera-Lastra O , Medina G , Cruz-Dominguez Mdel P , et al. Autoimmune/inflammatory syndrome induced by adjuvants (Shoenfeld’s syndrome): clinical and immunological spectrum. Expert Rev Clin Immunol 2013;9:361-73
   PubMed Web of Science ®Google Scholar
• Mills KH. TL R-dependent T cell activation in autoimmunity. Nat Rev Immunol 2011;11:807-22
   PubMed Web of Science ®Google Scholar
• Tacken PJ , Zeelenberg IS , Cruz LJ , et al. Targeted delivery of TLR ligands to human and mouse dendritic cells strongly enhances adjuvanticity. Blood 2011;118:6836-44
   PubMed Web of Science ®Google Scholar
• De Temmerman ML , Rejman J , Demeester J , et al. Particulate vaccines: on the quest for optimal delivery and immune response. Drug Discov Today 2011;16:569-82
   PubMed Web of Science ®Google Scholar
• Jain S , O’Hagan DT , Singh M . The long-term potential of biodegradable poly(lactide-co-glycolide) microparticles as the next-generation vaccine adjuvant. Expert Rev Vaccines 2011;10:1731-42
   PubMed Web of Science ®Google Scholar
• Katare YK , Muthukumaran T , Panda AK . Influence of particle size, antigen load, dose and additional adjuvant on the immune response from antigen loaded PLA microparticles. Int J Pharm 2005;301:149-60
   PubMed Web of Science ®Google Scholar
• Reece JC , Vardaxis NJ , Marshall JA , et al. Uptake of HIV and latex particles by fresh and cultured dendritic cells and monocytes. Immunol Cell Biol 2001;79:255-63
   PubMed Web of Science ®Google Scholar
• Manolova V , Flace A , Bauer M , et al. Nanoparticles target distinct dendritic cell populations according to their size. Eur J Immunol 2008;38:1404-13
   PubMed Web of Science ®Google Scholar
• Rosenthal JA , Chen L , Baker JL , et al. Pathogen-like particles: biomimetic vaccine carriers engineered at the nanoscale. Curr Opin Biotechnol 2013;28C:51-8
   Google Scholar
• Kwon YJ , James E , Shastri N , et al. In vivo targeting of dendritic cells for activation of cellular immunity using vaccine carriers based on pH-responsive microparticles. Proc Natl Acad Sci USA 2005;102:18264-8
   PubMed Web of Science ®Google Scholar
• Bandyopadhyay A , Fine RL , Demento S , et al. The impact of nanoparticle ligand density on dendritic-cell targeted vaccines. Biomaterials 2011;32:3094-105
   PubMed Web of Science ®Google Scholar
• Raghuwanshi D , Mishra V , Das D , et al. Dendritic cell targeted chitosan nanoparticles for nasal DNA immunization against SARS CoV nucleocapsid protein. Mol Pharm 2012;9:946-56
   PubMed Web of Science ®Google Scholar
• Scallan CD , Tingley DW , Lindbloom JD , et al. An adenovirus-based vaccine with a double-stranded RNA adjuvant protects mice and ferrets against H5N1 avian influenza in oral delivery models. Clin Vaccine Immunol 2013;20:85-94
   PubMed Web of Science ®Google Scholar
• Peters W , Brandl JR , Lindbloom JD , et al. Oral administration of an adenovirus vector encoding both an avian influenza A hemagglutinin and a TLR3 ligand induces antigen specific granzyme B and IFN-gamma T cell responses in humans. Vaccine 2013;31:1752-8
   PubMed Web of Science ®Google Scholar
• Joshi VB , Geary SM , Salem AK . Biodegradable particles as vaccine delivery systems: size matters. AAPS J 2013;15:85-94
   PubMed Web of Science ®Google Scholar
• Mutwiri G , Gerdts V , van Drunen Littel-van den Hurk S , et al. Combination adjuvants: the next generation of adjuvants? Expert Rev Vaccines 2011;10:95-107
   PubMed Web of Science ®Google Scholar
• Zhang XQ , Dahle CE , Weiner GJ , et al. A comparative study of the antigen-specific immune response induced by co-delivery of CpG ODN and antigen using fusion molecules or biodegradable microparticles. J Pharm Sci 2007;96:3283-92
   PubMed Web of Science ®Google Scholar
• Schlosser E , Mueller M , Fischer S , et al. TLR ligands and antigen need to be coencapsulated into the same biodegradable microsphere for the generation of potent cytotoxic T lymphocyte responses. Vaccine 2008;26:1626-37
   PubMed Web of Science ®Google Scholar
• Ilyinskii PO , Roy CJ , O’Neil CP , et al. Adjuvant-carrying synthetic vaccine particles augment the immune response to encapsulated antigen and exhibit strong local immune activation without inducing systemic cytokine release. Vaccine 2014;32:2882-95
   PubMed Web of Science ®Google Scholar
• Li Y , Hu Y , Jin Y , et al. Prophylactic, therapeutic and immune enhancement effect of liposome-encapsulated PolyICLC on highly pathogenic H5N1 influenza infection. J Gene Med 2011;13:60-72
   PubMed Web of Science ®Google Scholar
• Wong JP , Yang H , Nagata L , et al. Liposome-mediated immunotherapy against respiratory influenza virus infection using double-stranded RNA poly ICLC. Vaccine 1999;17:1788-95
   PubMed Web of Science ®Google Scholar
• Tough DF . Modulation of T-cell function by type I interferon. Immunol Cell Biol 2012;90:492-7
   PubMed Web of Science ®Google Scholar
• Dondi E , Rogge L , Lutfalla G , et al. Down-modulation of responses to type I IFN upon T cell activation. J Immunol 2003;170:749-56
   PubMed Web of Science ®Google Scholar
• Dondi E , Roue G , Yuste VJ , et al. A dual role of IFN-alpha in the balance between proliferation and death of human CD4+ T lymphocytes during primary response. J Immunol 2004;173:3740-7
   PubMed Web of Science ®Google Scholar
• Marshall HD , Urban SL , Welsh RM . Virus-induced transient immune suppression and the inhibition of T cell proliferation by type I interferon. J Virol 2011;85:5929-39
   PubMed Web of Science ®Google Scholar
• Lampkin BC , Levine AS , Levy H , et al. Phase II trial of a complex polyriboinosinic-polyribocytidylic acid with poly-L-lysine and carboxymethyl cellulose in the treatment of children with acute leukemia and neuroblastoma: a report from the Children’s Cancer Study Group. Cancer Res 1985;45:5904-9
   PubMed Web of Science ®Google Scholar
• Levine AS , Sivulich M , Wiernik PH , et al. Initial clinical trials in cancer patients of polyriboinosinic-polyribocytidylic acid stabilized with poly-L-lysine, in carboxymethylcellulose [poly(ICLC)], a highly effective interferon inducer. Cancer Res 1979;39:1645-50
   PubMed Web of Science ®Google Scholar