{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T04:39:47Z","timestamp":1776400787942,"version":"3.51.2"},"reference-count":77,"publisher":"American Society for Microbiology","issue":"14","license":[{"start":{"date-parts":[[2015,7,15]],"date-time":"2015-07-15T00:00:00Z","timestamp":1436918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2015,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Influenza virus can cause life-threatening infections in neonates and young infants. Although vaccination is a major countermeasure against influenza, current vaccines are not approved for use in infants less than 6 months of age, in part due to the weak immune response following vaccination. Thus, there is a strong need to develop new vaccines with improved efficacy for this vulnerable population. To address this issue, we established a neonatal African green monkey (AGM) nonhuman primate model that could be used to identify effective influenza vaccine approaches for use in young infants. We assessed the ability of flagellin, a Toll-like receptor 5 (TLR5) agonist, to serve as an effective adjuvant in this at-risk population. Four- to 6-day-old AGMs were primed and boosted with inactivated PR8 influenza virus (IPR8) adjuvanted with either wild-type flagellin or inactive flagellin with a mutation at position 229 (m229), the latter of which is incapable of signaling through TLR5. Increased IgG responses were observed following a boost, as well as at early times after challenge, in infants vaccinated with flagellin-adjuvanted IPR8. Inclusion of flagellin during vaccination also resulted in a significantly increased number of influenza virus-specific T cells following challenge compared to the number in infants vaccinated with the m229 adjuvant. Finally, following challenge infants vaccinated with IPR8 plus flagellin exhibited a reduced pathology in the lungs compared to that in infants that received IPR8 plus m229. This study provides the first evidence of flagellin-mediated enhancement of vaccine responses in nonhuman primate neonates.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>Young infants are particularly susceptible to severe disease as a result of influenza virus infection. Compounding this is the lack of effective vaccines for use in this vulnerable population. Here we describe a vaccine approach that results in improved immune responses and protection in young infants. Incorporation of flagellin during vaccination resulted in increased antibody and T cell responses together with reduced disease following virus infection. These results suggest that flagellin may serve as an effective adjuvant for vaccines targeted to this vulnerable population.<\/jats:p>","DOI":"10.1128\/jvi.00549-15","type":"journal-article","created":{"date-parts":[[2015,5,7]],"date-time":"2015-05-07T02:22:27Z","timestamp":1430965347000},"page":"7291-7303","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":35,"title":["Inclusion of Flagellin during Vaccination against Influenza Enhances Recall Responses in Nonhuman Primate Neonates"],"prefix":"10.1128","volume":"89","author":[{"given":"Jong R.","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beth C.","family":"Holbrook","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah L.","family":"Hayward","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lance K.","family":"Blevins","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew J.","family":"Jorgensen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy D.","family":"Kock","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina","family":"De Paris","sequence":"additional","affiliation":[{"name":"University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Ralph B.","family":"D'Agostino","sequence":"additional","affiliation":[{"name":"Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. Tyler","family":"Aycock","sequence":"additional","affiliation":[{"name":"Animal Resources Program, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven B.","family":"Mizel","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Griffith D.","family":"Parks","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martha A.","family":"Alexander-Miller","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006454-199711000-00012"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b3172"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.87.6.823"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/587643"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006454-200108000-00004"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1394"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2009.09.002"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0b013e32835fb8bf"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0032-1333412"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838391"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003934"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.21.10006"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2005.10.027"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117677"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.4049\/jimmunol.163.5.2416","article-title":"Inefficient phospholipase C activation and reduced Lck expression characterize the signaling defect of umbilical cord T lymphocytes","volume":"163","author":"Miscia S","year":"1999","unstructured":"Miscia S, Di Baldassarre A, Sabatino G, Bonvini E, Rana RA, Vitale M, Di Valerio V, Manzoli FA. 1999. Inefficient phospholipase C activation and reduced Lck expression characterize the signaling defect of umbilical cord T lymphocytes. J Immunol 163:2416\u20132424.","journal-title":"J Immunol"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202534"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903075"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200425333"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200636945"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002377"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(04)00072-X"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071371"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1203288"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.6.2824"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcpa.2007.04.004"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-01-069245"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-09-110858"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.3.1700"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.02.008"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903806"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.3.1556"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2014.12.007"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838620"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.08.002"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3409"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002156"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10482-013-0075-2"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.07.058"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.10.5165"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.182.1.55"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2008.01.009"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.08.009"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200636181"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200323797"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-621-0_3"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.10.5525-5529.2000"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.11.6676-6679.2004"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914994107"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.101.3.e3"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-04-494096"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2013.00328"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1201.051237"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/9.6.843"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1970"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.10035"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2008.05.001"},{"issue":"1","key":"e_1_3_2_58_2","first-page":"95","article-title":"Morphometric studies on the structural development of the lung in Macaca fascicularis during fetal and postnatal life","volume":"138","author":"Hislop A","year":"1984","unstructured":"Hislop A, Howard S, Fairweather DV. 1984. Morphometric studies on the structural development of the lung in Macaca fascicularis during fetal and postnatal life. J Anat 138(Pt 1):95\u2013112.","journal-title":"J Anat"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0923-2508(00)00227-8"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.2.1113-1120.2006"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2007.10.062"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00333-08"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.08.080"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0014442"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.05.041"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.10.009"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.05.001"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.3.1551"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.12.8051"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000863"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2009.03143.x"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2015.00017"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2013-3937"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0306147"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-10-4015"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2007.08.001"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09737"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1400478111"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00549-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00549-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T04:39:55Z","timestamp":1691642395000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.00549-15"}},"subtitle":[],"editor":[{"given":"S.","family":"Perlman","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2015,7,15]]},"references-count":77,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2015,7,15]]}},"alternative-id":["10.1128\/JVI.00549-15"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00549-15","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,15]]},"assertion":[{"value":"2015-02-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-04-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-06-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}