{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:43:24Z","timestamp":1789994604676,"version":"4.0.1"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2012,1,27]],"date-time":"2012-01-27T00:00:00Z","timestamp":1327622400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0030898","type":"journal-article","created":{"date-parts":[[2012,1,27]],"date-time":"2012-01-27T23:52:37Z","timestamp":1327708357000},"page":"e30898","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":74,"title":["Induction of Heterosubtypic Cross-Protection against Influenza by a Whole Inactivated Virus Vaccine: The Role of Viral Membrane Fusion Activity"],"prefix":"10.1371","volume":"7","author":[{"given":"Natalija","family":"Budimir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Huckriede","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tjarko","family":"Meijerhof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Boon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Gostick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Price","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Wilschut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aalzen","family":"de Haan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2012,1,27]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1016\/S0140-6736(03)14854-4","article-title":"Influenza.","volume":"362","author":"KG Nicholson","year":"2003","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1002\/(SICI)1096-9071(200005)61:1<94::AID-JMV15>3.0.CO;2-C","article-title":"Mismatch between the 1997\/1998 influenza vaccine and the major epidemic A(H3N2) virus strain as the cause of an inadequate vaccine-induced antibody response to this strain in the elderly.","volume":"61","author":"JC de Jong","year":"2000","journal-title":"J Med Virol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/ni1343","article-title":"Influenza and the challenge for immunology.","volume":"7","author":"PC Doherty","year":"2006","journal-title":"Nat Immunol"},{"key":"ref4","first-page":"3273","article-title":"Toward a broadly protective influenza vaccine.","volume":"118","author":"PC Doherty","year":"2008","journal-title":"J Clin Invest"},{"key":"ref5","first-page":"417","article-title":"Influenza nucleoprotein-specific cytotoxic T-cell clones are protective in vivo.","volume":"58","author":"PM Taylor","year":"1986","journal-title":"Immunology"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1586\/14787210.1.4.627","article-title":"Control of influenza virus infection by immunity to conserved viral features.","volume":"1","author":"SL Epstein","year":"2003","journal-title":"Expert Rev Anti Infect Ther"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1073\/pnas.82.6.1785","article-title":"Influenza A virus nucleoprotein is a major target antigen for cross-reactive anti-influenza A virus cytotoxic T lymphocytes.","volume":"82","author":"JW Yewdell","year":"1985","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"863985","DOI":"10.1155\/2010\/863985","article-title":"Controlling influenza by cytotoxic T-cells: calling for help from destroyers.","volume":"2010","author":"M Schotsaert","year":"2010","journal-title":"J Biomed Biotechnol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"e1190","DOI":"10.1371\/journal.pone.0001190","article-title":"Evolutionarily conserved protein sequences of influenza a viruses, avian and human, as vaccine targets.","volume":"2","author":"AT Heiny","year":"2007","journal-title":"PLoS One"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"8280","DOI":"10.1016\/j.vaccine.2010.10.007","article-title":"The role of membrane fusion activity of a whole inactivated influenza virus vaccine in (re)activation of influenza-specific cytotoxic T lymphocytes.","volume":"28","author":"N Budimir","journal-title":"Vaccine"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/0166-0934(91)90036-Y","article-title":"A study of the effect of chemical inactivants on the epitopes of Rift Valley fever virus glycoproteins using monoclonal antibodies.","volume":"33","author":"NK Blackburn","year":"1991","journal-title":"J Virol Methods"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1128\/JCM.26.8.1595-1597.1988","article-title":"Formalin-inactivated respiratory syncytial virus vaccine induces antibodies to the fusion glycoprotein that are deficient in fusion-inhibiting activity.","volume":"26","author":"BR Murphy","year":"1988","journal-title":"J Clin Microbiol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1111\/j.0105-2896.2005.00301.x","article-title":"Cross-presentation: underlying mechanisms and role in immune surveillance.","volume":"207","author":"KL Rock","year":"2005","journal-title":"Immunol Rev"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/j.1365-2567.2005.02268.x","article-title":"Enhanced and prolonged cross-presentation following endosomal escape of exogenous antigens encapsulated in biodegradable nanoparticles.","volume":"117","author":"H Shen","year":"2006","journal-title":"Immunology"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.1016\/j.vaccine.2005.04.026","article-title":"The virosome concept for influenza vaccines.","volume":"23","author":"A Huckriede","year":"2005","journal-title":"Vaccine"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"e14578","DOI":"10.1371\/journal.pone.0014578","article-title":"Production of inactivated influenza H5N1 vaccines from MDCK cells in serum-free medium.","volume":"6","author":"AY Hu","year":"2011","journal-title":"PLoS One"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1038\/nm1210-1389","article-title":"Induction of unnatural immunity: prospects for a broadly protective universal influenza vaccine.","volume":"16","author":"GJ Nabel","year":"2010","journal-title":"Nat Med"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1084\/jem.20101352","article-title":"Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection.","volume":"208","author":"J Wrammert","year":"2011","journal-title":"J Exp Med"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1371\/journal.pmed.0040059","article-title":"Cross-reactive neuraminidase antibodies afford partial protection against H5N1 in mice and are present in unexposed humans.","volume":"4","author":"MR Sandbulte","year":"2007","journal-title":"PLoS Med"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"9217","DOI":"10.1128\/JVI.01069-10","article-title":"Memory CD4 T cells direct protective responses to influenza virus in the lungs through helper-independent mechanisms.","volume":"84","author":"JR Teijaro","year":"2010","journal-title":"J Virol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/300655a0","article-title":"Influenza A specific cytotoxic T-cell clones that do not recognize viral glycoproteins.","volume":"300","author":"AR Townsend","year":"1982","journal-title":"Nature"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1084\/jem.160.2.552","article-title":"The influenza A virus nucleoprotein gene controls the induction of both subtype specific and cross-reactive cytotoxic T cells.","volume":"160","author":"AR Townsend","year":"1984","journal-title":"J Exp Med"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/296075a0","article-title":"A viral polymerase involved in recognition of influenza virus-infected cells by a cytotoxic T-cell clone.","volume":"296","author":"JR Bennink","year":"1982","journal-title":"Nature"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/sj.gt.3302673","article-title":"Reconstituted influenza virus envelopes as an efficient carrier system for cellular delivery of small-interfering RNAs.","volume":"13","author":"J de Jonge","year":"2006","journal-title":"Gene Ther"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1126\/science.1093616","article-title":"Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA.","volume":"303","author":"SS Diebold","year":"2004","journal-title":"Science"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"e1000138","DOI":"10.1371\/journal.ppat.1000138","article-title":"Superior immunogenicity of inactivated whole virus H5N1 influenza vaccine is primarily controlled by Toll-like receptor signalling.","volume":"4","author":"F Geeraedts","year":"2008","journal-title":"PLoS Pathog"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.copbio.2004.09.006","article-title":"Targeting split vaccines to the endosome improves vaccination.","volume":"15","author":"H Wagner","year":"2004","journal-title":"Curr Opin Biotechnol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.addr.2008.12.010","article-title":"The immunogenicity of CpG-antigen conjugates.","volume":"61","author":"H Wagner","year":"2009","journal-title":"Adv Drug Deliv Rev"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"3520","DOI":"10.1182\/blood-2002-10-3063","article-title":"Activation of influenza virus-specific CD4+ and CD8+ T cells: a new role for plasmacytoid dendritic cells in adaptive immunity.","volume":"101","author":"JF Fonteneau","year":"2003","journal-title":"Blood"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.coi.2010.01.022","article-title":"Intracellular mechanisms of antigen cross presentation in dendritic cells.","volume":"22","author":"S Amigorena","year":"2010","journal-title":"Curr Opin Immunol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0161-5890(02)00101-3","article-title":"Antigen degradation or presentation by MHC class I molecules via classical and non-classical pathways.","volume":"39","author":"M Gromme","year":"2002","journal-title":"Mol Immunol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/ni1082","article-title":"Cellular mechanisms governing cross-presentation of exogenous antigens.","volume":"5","author":"AL Ackerman","year":"2004","journal-title":"Nat Immunol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1084\/jem.182.6.1663","article-title":"Inactivated influenza virus, when presented on dendritic cells, elicits human CD8+ cytolytic T cell responses.","volume":"182","author":"A Bender","year":"1995","journal-title":"J Exp Med"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJM198307073090103","article-title":"Cytotoxic T-cell immunity to influenza.","volume":"309","author":"AJ McMichael","year":"1983","journal-title":"N Engl J Med"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"4212","DOI":"10.1128\/JVI.02508-09","article-title":"Cytotoxic T cells are the predominant players providing cross-protective immunity induced by {gamma}-irradiated influenza A viruses.","volume":"84","author":"Y Furuya","year":"2010","journal-title":"J Virol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1099\/vir.0.020784-0","article-title":"Vaccination with whole inactivated virus vaccine affects the induction of heterosubtypic immunity against influenza virus A\/H5N1 and immunodominance of virus-specific CD8+ T-cell responses in mice.","volume":"91","author":"R Bodewes","year":"2010","journal-title":"J Gen Virol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"e10818","DOI":"10.1371\/journal.pone.0010818","article-title":"Preferential amplification of CD8 effector-T cells after transcutaneous application of an inactivated influenza vaccine: a randomized phase I trial.","volume":"5","author":"B Combadiere","year":"2010","journal-title":"PLoS One"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.femsim.2004.09.003","article-title":"Evaluation of SIV-lipopeptide immunizations administered by the intradermal route in their ability to induce antigen specific T-cell responses in rhesus macaques.","volume":"43","author":"Z Coutsinos","year":"2005","journal-title":"FEMS Immunol Med Microbiol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1093\/jmcb\/mjq046","article-title":"Learning from the 2009 H1N1 pandemic: prospects for more broadly effective influenza vaccines.","volume":"3","author":"EC Settembre","year":"2011","journal-title":"J Mol Cell Biol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/j.1600-065X.2010.00974.x","article-title":"Influenza vaccine immunology.","volume":"239","author":"PR Dormitzer","year":"2011","journal-title":"Imm Rev"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1056\/NEJMoa0906612","article-title":"Clinical features of the initial cases of 2009 pandemic influenza A (H1N1) virus infection in China.","volume":"361","author":"B Cao","year":"2009","journal-title":"N Engl J Med"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"20365","DOI":"10.1073\/pnas.0911580106","article-title":"Pre-existing immunity against swine-origin H1N1 influenza viruses in the general human population.","volume":"106","author":"JA Greenbaum","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref43","first-page":"3478","article-title":"Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals.","volume":"118","author":"LY Lee","year":"2008","journal-title":"J Clin Invest"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"5161","DOI":"10.1128\/JVI.02694-07","article-title":"Cross-recognition of avian H5N1 influenza virus by human cytotoxic T-lymphocyte populations directed to human influenza A virus.","volume":"82","author":"JH Kreijtz","year":"2008","journal-title":"J Virol"},{"key":"ref45","first-page":"359","article-title":"Lessons learned from clinical trials in 1976 and 1977 of vaccines for the newly emerged swine and Russian influenza A\/H1N1 viruses.","author":"RB Couch","year":"2011"},{"key":"ref46","article-title":"European Pharmacopeia 01\/2005:0158."},{"key":"ref47","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1208\/s12248-010-9179-z","article-title":"Preservation of the immunogenicity of dry-powder influenza H5N1 whole inactivated virus vaccine at elevated storage temperatures.","volume":"12","author":"F Geeraedts","year":"2010","journal-title":"AAPS J"},{"key":"ref48","author":"EJ Hanon","year":"2008"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.1016\/j.vaccine.2008.02.063","article-title":"Alum boosts TH2-type antibody responses to whole-inactivated virus influenza vaccine in mice but does not confer superior protection.","volume":"26","author":"L Bungener","year":"2008","journal-title":"Vaccine"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/S0092-1157(81)80041-8","article-title":"Quantitative analysis of the protein composition of influenza A and B viruses using high resolution SDS polyacrylamide gels.","volume":"9","author":"JS Oxford","year":"1981","journal-title":"J Biol Stand"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1084\/jem.20051357","article-title":"Avidity for antigen shapes clonal dominance in CD8+ T cell populations specific for persistent DNA viruses.","volume":"202","author":"DA Price","year":"2005","journal-title":"J Exp Med"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0030898","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T09:42:30Z","timestamp":1593596550000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0030898"}},"subtitle":[],"editor":[{"given":"Man-Seong","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2012,1,27]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2012,1,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0030898","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1,27]]}}}