{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T23:30:42Z","timestamp":1774999842030,"version":"3.50.1"},"reference-count":50,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"name":"SPARKS Medical Research, UK","award":["12Liv01"],"award-info":[{"award-number":["12Liv01"]}]},{"DOI":"10.13039\/501100000374","name":"British Medical Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000374","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Royal Embassy of Saudi Arabia Culture Bureau"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Research"],"published-print":{"date-parts":[[2016,8]]},"DOI":"10.1016\/j.antiviral.2016.05.021","type":"journal-article","created":{"date-parts":[[2016,5,29]],"date-time":"2016-05-29T03:19:08Z","timestamp":1464491948000},"page":"122-130","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":14,"special_numbering":"C","title":["A critical role of T follicular helper cells in human mucosal anti-influenza response that can be enhanced by immunological adjuvant CpG-DNA"],"prefix":"10.1016","volume":"132","author":[{"given":"A.N.","family":"Aljurayyan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Upile","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Beer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Vaughan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Achar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.S.","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.S.","family":"McNamara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.B.","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Q.","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.antiviral.2016.05.021_bib1","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.antiviral.2014.12.008","article-title":"Cross-reactive immunity against influenza viruses in children and adults following 2009 pandemic H1N1 infection","volume":"114","author":"Ahmed","year":"2015","journal-title":"Antivir. Res."},{"key":"10.1016\/j.antiviral.2016.05.021_bib2","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1056\/NEJMoa065368","article-title":"Live attenuated versus inactivated influenza vaccine in infants and young children","volume":"356","author":"Belshe","year":"2007","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.antiviral.2016.05.021_bib3","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3005191","article-title":"Induction of ICOS+CXCR3+CXCR5+ TH cells correlates with antibody responses to influenza vaccination","volume":"5","author":"Bentebibel","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.antiviral.2016.05.021_bib4","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/S0002-9440(10)64841-9","article-title":"Human nasopharyngeal-associated lymphoreticular tissues. Functional analysis of subepithelial and intraepithelial B and T cells from adenoids and tonsils","volume":"157","author":"Boyaka","year":"2000","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib5","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1164\/rccm.201011-1783OC","article-title":"Potential of nasopharynx-associated lymphoid tissue for vaccine responses in the airways","volume":"183","author":"Brandtzaeg","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.antiviral.2016.05.021_bib6","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1084\/jem.192.11.1545","article-title":"Follicular B helper T cells express cxc chemokine receptor 5, Localize to B Cell follicles, and support immunoglobulin production","volume":"192","author":"Breitfeld","year":"2000","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.antiviral.2016.05.021_bib7","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1002\/emmm.201403841","article-title":"Monocyte-derived dendritic cells promote T follicular helper cell differentiation","volume":"6","author":"Chakarov","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.antiviral.2016.05.021_bib8","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.immuni.2011.03.023","article-title":"ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6","volume":"34","author":"Choi","year":"2011","journal-title":"Immunity"},{"key":"10.1016\/j.antiviral.2016.05.021_bib9","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1146\/annurev-immunol-031210-101400","article-title":"Follicular helper CD4 T Cells (TFH)","volume":"29","author":"Crotty","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib10","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.immuni.2014.10.004","article-title":"T\u00a0follicular helper cell differentiation, function, and roles in disease","volume":"41","author":"Crotty","year":"2014","journal-title":"Immunity"},{"key":"10.1016\/j.antiviral.2016.05.021_bib11","doi-asserted-by":"crossref","first-page":"2464","DOI":"10.1172\/JCI60945","article-title":"Plasmacytoid dendritic cells promote rotavirus-induced human and murine B cell responses","volume":"123","author":"Deal","year":"2013","journal-title":"J.\u00a0Clin. Investig."},{"key":"10.1016\/j.antiviral.2016.05.021_bib12","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/ni.1704","article-title":"The function of follicular helper T cells is regulated by the strength of T cell antigen receptor binding","volume":"10","author":"Fazilleau","year":"2009","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib13","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.4049\/jimmunol.1100853","article-title":"Cutting edge: dendritic cell-restricted antigen presentation initiates the follicular helper T cell program but cannot complete ultimate effector differentiation","volume":"187","author":"Goenka","year":"2011","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib14","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/mi.2013.89","article-title":"Activation of memory Th17 cells by domain 4 pneumolysin in human nasopharynx-associated lymphoid tissue and its association with pneumococcal carriage","volume":"7","author":"Gray","year":"2014","journal-title":"Mucosal Immunol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib15","doi-asserted-by":"crossref","first-page":"4531","DOI":"10.4049\/jimmunol.168.9.4531","article-title":"Quantitative expression of toll-like receptor 1\u201310 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides","volume":"168","author":"Hornung","year":"2002","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib16","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S1074-7613(03)00208-5","article-title":"Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6","volume":"19","author":"Jego","year":"2003","journal-title":"Immunity"},{"key":"10.1016\/j.antiviral.2016.05.021_bib17","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.immuni.2011.03.024","article-title":"Germinal center B Cell and T Follicular helper cell development initiates in the interfollicular zone","volume":"34","author":"Kerfoot","year":"2011","journal-title":"Immunity"},{"key":"10.1016\/j.antiviral.2016.05.021_bib18","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1084\/jem.193.12.1373","article-title":"Subspecialization of CXCR5+ T cells: B helper activity is focused in a germinal center-localized subset of CXCR5+ T cells","volume":"193","author":"Kim","year":"2001","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.antiviral.2016.05.021_bib19","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/nri2644","article-title":"New insights into the differentiation and function of T follicular helper cells","volume":"9","author":"King","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib20","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/nri1439","article-title":"NALT- versus Peyer\u2019s-patch-mediated mucosal immunity. [Review] [102 refs]","volume":"4","author":"Kiyono","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib21","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1080\/08830180600743057","article-title":"Adjuvant activity of CpG oligodeoxynucleotides","volume":"25","author":"Klinman","year":"2006","journal-title":"Int. Rev. Immunol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib22","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/374546a0","article-title":"CpG motifs in bacterial DNA trigger direct B-cell activation","volume":"374","author":"Krieg","year":"1995","journal-title":"Nature"},{"key":"10.1016\/j.antiviral.2016.05.021_bib23","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1002\/1521-4141(200107)31:7<2154::AID-IMMU2154>3.0.CO;2-U","article-title":"Identification of CpG oligonucleotide sequences with high induction of IFN-\u03b1\/\u03b2 in plasmacytoid dendritic cells","volume":"31","author":"Krug","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib24","doi-asserted-by":"crossref","first-page":"3026","DOI":"10.1002\/1521-4141(2001010)31:10<3026::AID-IMMU3026>3.0.CO;2-H","article-title":"Toll-like receptor expression reveals CpG DNA as a unique microbial stimulus for plasmacytoid dendritic cells which synergizes with CD40 ligand to induce high amounts of IL-12","volume":"31","author":"Krug","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib25","doi-asserted-by":"crossref","first-page":"356","DOI":"10.3324\/haematol.2009.019133","article-title":"A\u00a0novel subset of T-helper cells: follicular T-helper cells and their markers","volume":"95","author":"Laurent","year":"2010","journal-title":"Haematologica"},{"key":"10.1016\/j.antiviral.2016.05.021_bib26","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1038\/nri3251","article-title":"Recent progress in mucosal vaccine development: potential and limitations","volume":"12","author":"Lycke","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib27","doi-asserted-by":"crossref","first-page":"5331","DOI":"10.1128\/JVI.03547-12","article-title":"Infection with 2009 H1N1 influenza virus primes for immunological memory in human nose-associated lymphoid tissue, offering cross-reactive immunity to H1N1 and avian H5N1 viruses","volume":"87","author":"Mahallawi","year":"2013","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib28","doi-asserted-by":"crossref","first-page":"5764","DOI":"10.4049\/jimmunol.1201143","article-title":"Environmental and T Cell\u2013Intrinsic factors limit the expansion of neonatal follicular T helper cells but may Be circumvented by specific adjuvants","volume":"189","author":"Mastelic","year":"2012","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib29","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0264-410X(99)00194-2","article-title":"CpG DNA as mucosal adjuvant","volume":"18","author":"McCluskie","year":"1999","journal-title":"Vaccine"},{"key":"10.1016\/j.antiviral.2016.05.021_bib30","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/0264-410X(95)00016-T","article-title":"Human immune responses to influenza virus vaccines administered by systemic or mucosal routes","volume":"13","author":"Moldoveanu","year":"1995","journal-title":"Vaccine"},{"key":"10.1016\/j.antiviral.2016.05.021_bib31","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1016\/S0264-410X(98)80122-9","article-title":"CpG DNA, a novel immune enhancer for systemic and mucosal immunization with influenza virus","volume":"16","author":"Moldoveanu","year":"1998","journal-title":"Vaccine"},{"key":"10.1016\/j.antiviral.2016.05.021_bib32","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1016\/S0140-6736(00)05066-2","article-title":"Safety and antigenicity of non-adjuvanted and MF59-adjuvanted influenza A\/Duck\/Singapore\/97 (H5N3) vaccine: a randomised trial of two potential vaccines against H5N1 influenza","volume":"357","author":"Nicholson","year":"2001","journal-title":"Lancet"},{"key":"10.1016\/j.antiviral.2016.05.021_bib33","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1471-2172-9-10","article-title":"Activation of tonsil dendritic cells with immuno-adjuvants","volume":"9","author":"Polak","year":"2008","journal-title":"BMC Immunol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib34","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1002\/eji.200636136","article-title":"Follicular B helper T cell activity is confined to CXCR5hiICOShi CD4 T cells and is independent of CD57 expression","volume":"36","author":"Rasheed","year":"2006","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib35","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1002\/eji.201343533","article-title":"Plasmacytoid DCs are gentle guardians of tonsillar epithelium","volume":"43","author":"Rescigno","year":"2013","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib36","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.4049\/jimmunol.1102786","article-title":"Cutting Edge: IL-21 derived from human follicular helper T cells acts as a survival factor for secondary lymphoid organ, but not for bone marrow, plasma cells","volume":"188","author":"Rodr\u00edguez-Bayona","year":"2012","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib37","doi-asserted-by":"crossref","first-page":"E3224","DOI":"10.1073\/pnas.1323985111","article-title":"Toll-like receptor 9 signaling acts on multiple elements of the germinal center to enhance antibody responses","volume":"111","author":"Rookhuizen","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.antiviral.2016.05.021_bib38","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/S0198-8859(02)00749-8","article-title":"Plasmacytoid dendritic cells: the key to CpG","volume":"63","author":"Rothenfusser","year":"2002","journal-title":"Hum. Immunol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib39","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1084\/jem.192.11.1553","article-title":"Cxc chemokine receptor 5 expression defines follicular homing T Cells with B Cell helper function","volume":"192","author":"Schaerli","year":"2000","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.antiviral.2016.05.021_bib40","doi-asserted-by":"crossref","unstructured":"Schmitt, N., Ueno, H., Blood TFH cells come with colors. Immunity 39, 629\u2013630.","DOI":"10.1016\/j.immuni.2013.09.011"},{"key":"10.1016\/j.antiviral.2016.05.021_bib41","series-title":"Vaccines","first-page":"14","article-title":"2-Vaccine immunology","author":"Siegrist","year":"2013"},{"key":"10.1016\/j.antiviral.2016.05.021_bib42","first-page":"712","article-title":"CXCR5(+) T helper cells mediate protective immunity against tuberculosis","volume":"123","author":"Slight","year":"2013","journal-title":"J.\u00a0Clin. Investig."},{"key":"10.1016\/j.antiviral.2016.05.021_bib43","doi-asserted-by":"crossref","first-page":"14330","DOI":"10.1073\/pnas.1311998110","article-title":"Human circulating influenza-CD4+ ICOS1+IL-21+ T cells expand after vaccination, exert helper function, and predict antibody responses","volume":"110","author":"Spensieri","year":"2013","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.antiviral.2016.05.021_bib44","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3390\/vaccines3020373","article-title":"Influenza vaccination strategies: comparing inactivated and live attenuated influenza vaccines","volume":"3","author":"Sridhar","year":"2015","journal-title":"Vaccines"},{"key":"10.1016\/j.antiviral.2016.05.021_bib45","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0002-9440(10)61694-X","article-title":"Phenotypic characterization of five dendritic cell subsets in human tonsils","volume":"159","author":"Summers","year":"2001","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib46","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1016\/S0264-410X(99)00526-5","article-title":"CpG DNA induces stronger immune responses with less toxicity than other adjuvants","volume":"18","author":"Weeratna","year":"2000","journal-title":"Vaccine"},{"key":"10.1016\/j.antiviral.2016.05.021_bib47","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0092-1157(77)80008-5","article-title":"An improved single-radial-immunodiffusion technique for the assay of influenza haemagglutinin antigen: application for potency determinations of inactivated whole virus and subunit vaccines","volume":"5","author":"Wood","year":"1977","journal-title":"J.\u00a0Biol. Stand"},{"key":"10.1016\/j.antiviral.2016.05.021_bib48","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1086\/512617","article-title":"Low CD4 T cell immunity to pneumolysin is associated with nasopharyngeal carriage of pneumococci in children","volume":"195","author":"Zhang","year":"2007","journal-title":"J.\u00a0Infect. Dis."},{"key":"10.1016\/j.antiviral.2016.05.021_bib49","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/eji.200535101","article-title":"Serum and mucosal antibody responses to pneumococcal protein antigens in children: relationships with carriage status","volume":"36","author":"Zhang","year":"2006","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.antiviral.2016.05.021_bib50","doi-asserted-by":"crossref","first-page":"e1002175","DOI":"10.1371\/journal.ppat.1002175","article-title":"Characterisation of regulatory T cells in nasal associated lymphoid tissue in children: relationships with pneumococcal colonization","volume":"7","author":"Zhang","year":"2011","journal-title":"PLoS Pathog."}],"container-title":["Antiviral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0166354216301292?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0166354216301292?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T21:03:16Z","timestamp":1567976596000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0166354216301292"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8]]},"references-count":50,"alternative-id":["S0166354216301292"],"URL":"https:\/\/doi.org\/10.1016\/j.antiviral.2016.05.021","relation":{},"ISSN":["0166-3542"],"issn-type":[{"value":"0166-3542","type":"print"}],"subject":[],"published":{"date-parts":[[2016,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A critical role of T follicular helper cells in human mucosal anti-influenza response that can be enhanced by immunological adjuvant CpG-DNA","name":"articletitle","label":"Article Title"},{"value":"Antiviral Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.antiviral.2016.05.021","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"}]}}