{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T05:44:38Z","timestamp":1769147078790,"version":"3.49.0"},"reference-count":48,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmaceutics and Biopharmaceutics"],"published-print":{"date-parts":[[2016,10]]},"DOI":"10.1016\/j.ejpb.2016.07.004","type":"journal-article","created":{"date-parts":[[2016,7,5]],"date-time":"2016-07-05T02:35:30Z","timestamp":1467686130000},"page":"110-119","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":22,"special_numbering":"C","title":["The adjuvant effect of TLR7 agonist conjugated to a meningococcal serogroup C glycoconjugate vaccine"],"prefix":"10.1016","volume":"107","author":[{"given":"Agnese","family":"Donadei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristiana","family":"Balocchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Mancini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Proietti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Gallorini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek T.","family":"O\u2019Hagan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ugo","family":"D\u2019Oro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Berti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara C.","family":"Baudner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Adamo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejpb.2016.07.004_b0005","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/nature09737","article-title":"Programming the magnitude and persistence of antibody responses with innate immunity","volume":"470","author":"Kasturi","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.ejpb.2016.07.004_b0010","doi-asserted-by":"crossref","first-page":"7119","DOI":"10.1158\/1078-0432.CCR-07-1443","article-title":"First in human phase I trial of 852A, a novel systemic toll-like receptor 7 agonist, to activate innate immune responses in patients with advanced cancer","volume":"13","author":"Dudek","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ejpb.2016.07.004_b0015","doi-asserted-by":"crossref","first-page":"3561","DOI":"10.1021\/jm00047a014","article-title":"Small-molecule immunostimulants. Synthesis and activity of 7,8-disubstituted guanosines and structurally related compounds","volume":"37","author":"Reitz","year":"1994","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejpb.2016.07.004_b0020","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.bmc.2003.12.008","article-title":"Synthesis and evaluation of 2-substituted 8-hydroxyadenines as potent interferon inducers with improved oral bioavailabilities","volume":"12","author":"Kurimoto","year":"2004","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejpb.2016.07.004_b0025","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.1021\/jm100070n","article-title":"Synthesis and biological evaluation of 8-oxoadenine derivatives as tolllike receptor 7 agonists introducing the antedrug concept","volume":"53","author":"Kurimoto","year":"2010","journal-title":"J. Med. Chem. Biol."},{"key":"10.1016\/j.ejpb.2016.07.004_b0030","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1021\/bc900054q","article-title":"Synthesis and immunological characterization of Toll-like receptor 7 agonistic conjugates","volume":"20","author":"Chan","year":"2009","journal-title":"Bioconjugate Chem."},{"key":"10.1016\/j.ejpb.2016.07.004_b0035","doi-asserted-by":"crossref","first-page":"3990","DOI":"10.1073\/pnas.0611624104","article-title":"Immunotherapeutic activity of a conjugate of a Toll-like receptor 7 ligand","volume":"104","author":"Wu","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ejpb.2016.07.004_b0040","doi-asserted-by":"crossref","first-page":"263ra160","DOI":"10.1126\/scitranslmed.3009980","article-title":"Rational design of small molecules as vaccine adjuvants","volume":"6","author":"Wu","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ejpb.2016.07.004_b0045","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1586\/erv.11.26","article-title":"TLR-7 and -8 agonists as vaccine adjuvants","volume":"10","author":"Tomai","year":"2011","journal-title":"Expert Rev. Vaccines"},{"key":"10.1016\/j.ejpb.2016.07.004_b0050","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1016\/j.vaccine.2005.10.045","article-title":"Topical imiquimod is a potent adjuvant to a weakly immunogenic protein prototype vaccine","volume":"24","author":"Johnston","year":"2006","journal-title":"Vaccine"},{"key":"10.1016\/j.ejpb.2016.07.004_b0055","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1128\/IAI.00974-08","article-title":"Enhanced immunogenicity of Plasmodium falciparum peptide vaccines using a topical adjuvant containing a potent synthetic Toll-Like Receptor 7 agonist, Imiquimod","volume":"77","author":"Othoro","year":"2009","journal-title":"Infect. Immun."},{"key":"10.1016\/j.ejpb.2016.07.004_b0060","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1378\/chest.121.4.1329","article-title":"Cardiac inflammation and innate immunity in septic shock: is there a role for toll-like receptors?","volume":"121","author":"Knuefermann","year":"2002","journal-title":"Chest"},{"key":"10.1016\/j.ejpb.2016.07.004_b0065","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.jhep.2007.02.025","article-title":"Oral resiquimod in chronic HCV infection: safety and efficacy in 2 placebo-controlled, doubleblind phase IIa studies","volume":"47","author":"Pockros","year":"2007","journal-title":"J. Hepatol."},{"key":"10.1016\/j.ejpb.2016.07.004_b0070","doi-asserted-by":"crossref","first-page":"3846","DOI":"10.1128\/AAC.47.12.3846-3852.2003","article-title":"Randomized, single-blind, placebo-controlled study of topical application of the immune response modulator resiquimod in healthy adults","volume":"47","author":"Sauder","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejpb.2016.07.004_b0075","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1021\/acs.bioconjchem.5b00285","article-title":"Enhancement of the immunostimulatory activity of a TLR7 ligand by conjugation to polysaccharides","volume":"25","author":"Shinchi","year":"2015","journal-title":"Bioconjugate Chem."},{"key":"10.1016\/j.ejpb.2016.07.004_b0080","doi-asserted-by":"crossref","first-page":"19008","DOI":"10.1074\/jbc.M311618200","article-title":"Ligand-regulated chimeric receptor approach reveals distinctive subcellular localization and signaling properties of the Toll-like receptors","volume":"279","author":"Nishiya","year":"2004","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejpb.2016.07.004_b0085","first-page":"5683","article-title":"Small molecule Toll-like receptor 7 agonists localize to the MHC class II loading compartment of human plasmacytoid dendritic cells","volume":"127","author":"Russo","year":"2013","journal-title":"Blood"},{"key":"10.1016\/j.ejpb.2016.07.004_b0090","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.jconrel.2011.12.039","article-title":"Towards tailored vaccine delivery: needs, challenges and perspectives","volume":"20","author":"Amorji","year":"2012","journal-title":"J. Control. Release"},{"key":"10.1016\/j.ejpb.2016.07.004_b0095","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1007\/s00262-006-0262-3","article-title":"TLR7 imidazoquinoline ligand 3M-019 is a potent adjuvant for pure protein prototype vaccines","volume":"56","author":"Johnston","year":"2007","journal-title":"Cancer Immunol. Immunother."},{"key":"10.1016\/j.ejpb.2016.07.004_b0100","doi-asserted-by":"crossref","first-page":"15190","DOI":"10.1073\/pnas.0507484102","article-title":"HIV Gag protein conjugated to a Toll-like receptor 7\/8 agonist improves the magnitude and quality of Th1 and CD8+ T cell responses in nonhuman primates","volume":"102","author":"Wille-Reece","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ejpb.2016.07.004_b0105","doi-asserted-by":"crossref","first-page":"7676","DOI":"10.4049\/jimmunol.174.12.7676","article-title":"Immunization with HIV-1 Gag protein conjugated to a TLR7\/8 agonist results in the generation of HIV-1 gag-specific Th1 and CD8 T cell responses","author":"Wille-Reece","year":"2005","journal-title":"J. Immunol."},{"key":"10.1016\/j.ejpb.2016.07.004_b0110","doi-asserted-by":"crossref","first-page":"4602","DOI":"10.4049\/jimmunol.1001892","article-title":"The capacity to induce cross-presentation dictates the success of a TLR7 agonist-conjugate vaccine for eliciting cellular immunity","volume":"185","author":"Oh","year":"2010","journal-title":"J. Immunol."},{"key":"10.1016\/j.ejpb.2016.07.004_b0115","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.ejpb.2014.01.002","article-title":"Conjugation of a TLR7 agonist and antigen enhances protection in the S. pneumoniae murine infection model","volume":"87","author":"Vecchi","year":"2014","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.ejpb.2016.07.004_b0120","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1517\/14712598.2012.725718","article-title":"Glycoconjugate vaccines","volume":"13","author":"Pace","year":"2013","journal-title":"Expert Opin. Biol. Ther."},{"key":"10.1016\/j.ejpb.2016.07.004_b0125","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1021\/cb400423g","article-title":"Recent mechanistic insights on glycoconjugate vaccines and future perspectives","volume":"8","author":"Berti","year":"2013","journal-title":"ACS Chem. Biol."},{"key":"10.1016\/j.ejpb.2016.07.004_b0130","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1086\/649209","article-title":"Changes in Neisseria meningitidis disease epidemiology in the United States, 1998\u20132007: implications for prevention of meningococcal disease","volume":"50","author":"Cohn","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"10.1016\/j.ejpb.2016.07.004_b0135","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.3201\/eid1911.130610","article-title":"Three outbreakcausing Neisseria meningitidis serogroup C clones, Brazil","volume":"19","author":"Barroso","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"10.1016\/j.ejpb.2016.07.004_b0140","unstructured":"http:\/\/www.cdc.gov\/meningococcal\/surveillance\/index.html."},{"key":"10.1016\/j.ejpb.2016.07.004_b0145","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1517\/17460441.2011.609554","article-title":"The design of semi-synthetic and synthetic glycoconjugate vaccines","volume":"6","author":"Costantino","year":"2011","journal-title":"Expert Opin. Drug Disc."},{"key":"10.1016\/j.ejpb.2016.07.004_b0150","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1007\/s10719-014-9559-1","article-title":"Investigating the immunodominance of carbohydrate antigens in a bivalent unimolecular glycoconjugate vaccine against serogroup A and C meningococcal disease","volume":"31","author":"Adamo","year":"2014","journal-title":"Glycocon. J."},{"key":"10.1016\/j.ejpb.2016.07.004_b0155","doi-asserted-by":"crossref","first-page":"7161","DOI":"10.1016\/S0021-9258(17)39586-8","article-title":"Labeling the granulocyte C5a receptor with a unique photoreactive probe","volume":"260","author":"Johnson","year":"1985","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejpb.2016.07.004_b0160","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1016\/j.vaccine.2008.01.022","article-title":"Physicochemical characterisation of glycoconjugate vaccines for prevention of meningococcal diseases","volume":"26","author":"Bardotti","year":"2009","journal-title":"Vaccine"},{"key":"10.1016\/j.ejpb.2016.07.004_b0165","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/jps.22759","article-title":"Aluminum adjuvant dose guidelines in vaccine formulation for preclinical evaluations","volume":"101","author":"Vecchi","year":"2012","journal-title":"J. Pharm. Sc."},{"key":"10.1016\/j.ejpb.2016.07.004_b0170","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1128\/IAI.73.2.1151-1160.2005","article-title":"The region comprising amino acids 100 to 255 of Neisseria meningitidis lipoprotein GNA 1870 elicits bactericidal antibodies","volume":"73","author":"Giuliani","year":"2005","journal-title":"Infect. Imm."},{"key":"10.1016\/j.ejpb.2016.07.004_b0175","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/0264-410X(92)90091-W","article-title":"Development and phase I clinical testing of a conjugate vaccine against meningococcus A and C","volume":"10","author":"Costantino","year":"1992","journal-title":"Vaccine"},{"key":"10.1016\/j.ejpb.2016.07.004_b0180","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1002\/cbic.201300785","article-title":"Defined conjugation of glycans to the lysines of CRM197 guided by their reactivity mapping","volume":"14","author":"Crotti","year":"2014","journal-title":"ChemBioChem"},{"key":"10.1016\/j.ejpb.2016.07.004_b0185","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1016\/j.vaccine.2004.01.037","article-title":"Resiquimod is a modest adjuvant for HIV-1 gag-based genetic immunization in a mouse model","volume":"22","author":"Otero","year":"2004","journal-title":"Vaccine"},{"key":"10.1016\/j.ejpb.2016.07.004_b0190","doi-asserted-by":"crossref","first-page":"5263","DOI":"10.1016\/j.vaccine.2005.06.024","article-title":"TLR agonists as vaccine adjuvants: comparison of CpG ODN and resiquimod (R-848)","volume":"23","author":"Weeratna","year":"2005","journal-title":"Vaccine"},{"key":"10.1016\/j.ejpb.2016.07.004_b0195","doi-asserted-by":"crossref","first-page":"4733","DOI":"10.4049\/jimmunol.172.8.4733","article-title":"A Toll-like receptor 2 ligand stimulates Th2 responses in vivo, via induction of extracellular signalregulated kinase mitogen-activated protein kinase and c-Fos in dendritic cells","volume":"172","author":"Dillon","year":"2004","journal-title":"J. Immunol."},{"key":"10.1016\/j.ejpb.2016.07.004_b0200","article-title":"Lower levels of IgG1 in comparison with IgG2a are associated with protective immunity against Leishmania tropica infection in BALB\/c mice","volume":"14","author":"Rostamian","year":"2015","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"10.1016\/j.ejpb.2016.07.004_b0205","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1128\/CVI.00156-06","article-title":"Distinct contributions of vaccine-induced immunoglobulin G1 (IgG1) and IgG2a antibodies to protective immunity against influenza","volume":"13","author":"Huber","year":"2006","journal-title":"Clin. Vacc. Immunol."},{"key":"10.1016\/j.ejpb.2016.07.004_b0210","doi-asserted-by":"crossref","first-page":"4403","DOI":"10.4049\/jimmunol.0900164","article-title":"Alum induces innate immune responses through macrophage and mast cell sensors, but these sensors are not required for alum to act as an adjuvant for specific immunity","volume":"183","author":"McKee","year":"2009","journal-title":"J. Immunol."},{"key":"10.1016\/j.ejpb.2016.07.004_b0215","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.0300-9475.2004.01362.x","article-title":"The four mouse IgG isotypes differ extensively in bactericidal and opsonophagocytic activity when reacting with the P1.16 epitope on the outer membrane PorA protein of Neisseria meningitidis","volume":"59","author":"Michaelsen","year":"2004","journal-title":"Scand. J. Immunol."},{"key":"10.1016\/j.ejpb.2016.07.004_b0220","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1128\/CVI.00529-09","article-title":"Updated postlicensure surveillance of the meningococcal C conjugate vaccine in England and Wales: effectiveness, validation of serological correlates of protection, and modeling predictions of the duration of herd immunity","volume":"17","author":"Campbell","year":"2010","journal-title":"Clin. Vaccine Immunol."},{"key":"10.1016\/j.ejpb.2016.07.004_b0225","doi-asserted-by":"crossref","first-page":"6456","DOI":"10.1016\/j.vaccine.2012.08.004","article-title":"Immunogenicity and safety of a new meningococcal A conjugate vaccine in Indian children aged 2\u201310 years: a phase II\/III double-blind randomized controlled trial","volume":"30","author":"Hirve","year":"2012","journal-title":"Vaccine"},{"key":"10.1016\/j.ejpb.2016.07.004_b0230","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1034\/j.1398-9995.2000.00501.x","article-title":"Aluminium-induced granulomas after inaccurate intradermal hyposensitization injections of aluminium-adsorbed depot preparations","volume":"55","author":"Vogelbruch","year":"2000","journal-title":"Allergy"},{"key":"10.1016\/j.ejpb.2016.07.004_b0235","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1517\/14712598.3.6.895","article-title":"Antigens onto bare skin: a \u2018painless\u2019 paradigm shift in vaccine deliver","volume":"3","author":"Partidos","year":"2003","journal-title":"Expert Opin. Biol. Ther."},{"key":"10.1016\/j.ejpb.2016.07.004_b0240","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1038\/nbt.2759","article-title":"Vaccine delivery with microneedle skin patches in nonhuman primates","volume":"31","author":"DeMuth","year":"2013","journal-title":"Nat. Biotechnol."}],"container-title":["European Journal of Pharmaceutics and Biopharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0939641116302673?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0939641116302673?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T02:20:55Z","timestamp":1718677255000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0939641116302673"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10]]},"references-count":48,"alternative-id":["S0939641116302673"],"URL":"https:\/\/doi.org\/10.1016\/j.ejpb.2016.07.004","relation":{},"ISSN":["0939-6411"],"issn-type":[{"value":"0939-6411","type":"print"}],"subject":[],"published":{"date-parts":[[2016,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The adjuvant effect of TLR7 agonist conjugated to a meningococcal serogroup C glycoconjugate vaccine","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmaceutics and Biopharmaceutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejpb.2016.07.004","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}