{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:31:05Z","timestamp":1787495465156,"version":"build-2736575974"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2017,6,5]],"date-time":"2017-06-05T00:00:00Z","timestamp":1496620800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T00:00:00Z","timestamp":1496275200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"GlaxoSmithKline Biologicals SA"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Clin Vaccine Immunol"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    We investigated the role of AS03\n                    <jats:sub>A<\/jats:sub>\n                    (here AS03), an \u03b1-tocopherol oil-in-water emulsion-based adjuvant system, on the long-term persistence of humoral and cell-mediated immune responses to A(H1N1)pdm09 influenza vaccines. In two studies, a total of 261 healthy adults (\u226460 years old) were randomized to receive two doses of AS03-adjuvanted vaccine containing 3.75 \u03bcg of hemagglutinin (HA) or nonadjuvanted vaccine containing 15 \u03bcg of hemagglutinin (in study A) or 3.75 \u03bcg of hemagglutinin (in study B) 21 days apart. Hemagglutination inhibition (HI) antibody, memory B-cell, and CD4\n                    <jats:sup>+<\/jats:sup>\n                    \/CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell responses were characterized up to 1 year following dose 1. We also assessed the effects of age and seasonal influenza vaccination history. AS03-adjuvanted (3.75 \u03bcg HA) vaccine and nonadjuvanted vaccine at 15 \u03bcg but not at 3.75 \u03bcg HA elicited HI antibody responses persisting at levels that continued to meet European licensure criteria through month 12. At month 12, the geometric mean titer for AS03-adjuvanted vaccine was similar to that for nonadjuvanted (15-\u03bcg) vaccine in study A (1:86 and 1:88, respectively) and higher than that for nonadjuvanted (3.75-\u03bcg) vaccine in study B (1:77 and 1:35, respectively). A(H1N1)pdm09-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell and B-cell responses were stronger in AS03-adjuvanted groups and persisted only in these groups for 12 months at levels exceeding prevaccination frequencies. Advancing age and a seasonal vaccination history tended to reduce HI antibody and memory B-cell responses and, albeit less consistently, CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell responses. Thus, AS03 seemed to enhance the persistence of humoral and cell-mediated responses to A(H1N1)pdm09 vaccine, allowing for antigen sparing and mitigating potential negative effects of age and previous seasonal vaccination. (These studies have been registered at ClinicalTrials.gov under registration no. NCT00968539 and NCT00989287.)\n                  <\/jats:p>","DOI":"10.1128\/cvi.00553-16","type":"journal-article","created":{"date-parts":[[2017,4,26]],"date-time":"2017-04-26T20:40:24Z","timestamp":1493239224000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Long-Term Persistence of Cell-Mediated and Humoral Responses to A(H1N1)pdm09 Influenza Virus Vaccines and the Role of the AS03 Adjuvant System in Adults during Two Randomized Controlled Trials"],"prefix":"10.1128","volume":"24","author":[{"given":"Robbert G.","family":"van der Most","sequence":"first","affiliation":[{"name":"GSK Vaccines, Rixensart, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Cl\u00e9ment","sequence":"additional","affiliation":[{"name":"Center for Vaccinology, Ghent University and University Hospital, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Willekens","sequence":"additional","affiliation":[{"name":"Center for Vaccinology, Ghent University and University Hospital, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walth\u00e8re","family":"Dew\u00e9","sequence":"additional","affiliation":[{"name":"GSK Vaccines, Rixensart, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Walravens","sequence":"additional","affiliation":[{"name":"GSK Vaccines, Rixensart, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Vaughn","sequence":"additional","affiliation":[{"name":"GSK Vaccines, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert","family":"Leroux-Roels","sequence":"additional","affiliation":[{"name":"Center for Vaccinology, Ghent University and University Hospital, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.05046-11"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.1911"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/655830"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.01.011"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2012.07.081"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00480-10"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000000709"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2013.15"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3008409"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2013.07.007"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.11.058"},{"key":"e_1_3_3_13_2","volume-title":"EMEA\/CHMP\/VWP\/263499\/2006","author":"European Medicines Agency Committee for Human Medicinal Products","year":"2007","unstructured":"European Medicines Agency Committee for Human Medicinal Products. 2007. Guideline on influenza vaccines prepared from viruses with the potential to cause a pandemic and intended for use outside of the core dossier context. EMEA\/CHMP\/VWP\/263499\/2006. European Medicines Agency, London, United Kingdom. http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Scientific_guideline\/2009\/09\/WC500003872.pdf."},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(10)70296-6"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-12-279"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis427"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir026"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.08.076"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.05053-11"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)62026-2"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.2011.00381.x"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.4161\/hv.24504"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu284"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900398"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912458109"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2015.0627"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.12.014"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0907413"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.4161\/hv.6.11.12851"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3328"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir641"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3000624"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002336"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.7.4.467"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0906453"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01460-06"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1321060111"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu066"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.90"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0149289"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2015.03.026"},{"key":"e_1_3_3_42_2","volume-title":"Narcolepsy in association with pandemic influenza vaccination\u2014a multi-country European epidemiological investigation","author":"European Centre for Disease Prevention and Control","year":"2012","unstructured":"European Centre for Disease Prevention and Control. 2012. Narcolepsy in association with pandemic influenza vaccination\u2014a multi-country European epidemiological investigation. ECDC, Stockholm, Sweden. http:\/\/ecdc.europa.eu\/en\/publications\/publications\/vaesco%20report%20final%20with%20cover.pdf."},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(13)70238-X"},{"key":"e_1_3_3_44_2","unstructured":"European Medicines Agency. 2015. Pandemrix\u2014European public assessment report (EPAR) EMA\/691037\/2013. Annex I: summary of product characteristics. http:\/\/www.ema.europa.eu\/ema\/index.jsp?curl=pages\/medicines\/human\/medicines\/000832\/human_med_000965.jsp&mid=WC0b01ac058001d124. Accessed 2 October 2016."},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.2165\/00044011-200222110-00004"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2003.12.015"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-010-9490-6"}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00553-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00553-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T11:43:32Z","timestamp":1627559012000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.00553-16"}},"subtitle":[],"editor":[{"given":"Kathryn M.","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,6]]},"references-count":46,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,6]]}},"alternative-id":["10.1128\/CVI.00553-16"],"URL":"https:\/\/doi.org\/10.1128\/cvi.00553-16","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6]]},"assertion":[{"value":"2016-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-04-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-06-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}