{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:15:55Z","timestamp":1790252155688,"version":"4.1.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T00:00:00Z","timestamp":1574121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Increasing evidence supports a critical role of CD8+ T-cell immunity against influenza. Activation of mucosal CD8+ T cells, particularly tissue-resident memory T (TRM) cells recognizing conserved epitopes would mediate rapid and broad protection. Matrix protein 1 (M1) is a well-conserved internal protein.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We studied the capacity of modified vaccinia Ankara (MVA)\u2013vectored vaccine expressing nucleoprotein (NP) and M1 (MVA-NP+M1) to activate M1-specific CD8+ T-cell response, including TRM cells, in nasopharynx-associated lymphoid tissue from children and adults.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>After MVA-NP+M1 stimulation, M1 was abundantly expressed in adenotonsillar epithelial cells and B cells. MVA-NP+M1 activated a marked interferon \u03b3\u2013secreting T-cell response to M1 peptides. Using tetramer staining, we showed the vaccine activated a marked increase in M158\u201366 peptide-specific CD8+ T cells in tonsillar mononuclear cells of HLA-matched individuals. We also demonstrated MVA-NP+M1 activated a substantial increase in TRM cells exhibiting effector memory T-cell phenotype. On recall antigen recognition, M1-specific T cells rapidly undergo cytotoxic degranulation, release granzyme B and proinflammatory cytokines, leading to target cell killing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>MVA-NP+M1 elicits a substantial M1-specific T-cell response, including TRM cells, in nasopharynx-associated lymphoid tissue, demonstrating its strong capacity to expand memory T-cell pool exhibiting effector memory T-cell phenotype, therefore offering great potential for rapid and broad protection against influenza reinfection.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiz593","type":"journal-article","created":{"date-parts":[[2019,11,13]],"date-time":"2019-11-13T20:09:37Z","timestamp":1573675777000},"page":"807-819","source":"Crossref","is-referenced-by-count":25,"title":["Modified Vaccinia Ankara\u2013Vectored Vaccine Expressing Nucleoprotein and Matrix Protein 1 (M1) Activates Mucosal M1-Specific T-Cell Immunity and Tissue-Resident Memory T Cells in Human Nasopharynx-Associated Lymphoid Tissue"],"prefix":"10.1093","volume":"222","author":[{"given":"Suttida","family":"Puksuriwong","sequence":"first","affiliation":[{"name":"Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad S","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Sharma","sequence":"additional","affiliation":[{"name":"ENT Departments, Alder Hey Children\u2019s Hospital, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhan","family":"Krishnan","sequence":"additional","affiliation":[{"name":"ENT Departments, Alder Hey Children\u2019s Hospital, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Leong","sequence":"additional","affiliation":[{"name":"ENT Departments, Aintree University Hospital, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Lambe","sequence":"additional","affiliation":[{"name":"The Jenner Institute, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S","family":"McNamara","sequence":"additional","affiliation":[{"name":"Institute of Child Health, Alder Hey Children\u2019s Hospital, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah C","family":"Gilbert","sequence":"additional","affiliation":[{"name":"The Jenner Institute, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qibo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,11,19]]},"reference":[{"key":"2020080404303713100_CIT0001","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/S1473-3099(11)70295-X","article-title":"Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis","volume":"12","author":"Osterholm","year":"2012","journal-title":"Lancet Infect Dis"},{"key":"2020080404303713100_CIT0002","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.virusres.2011.09.022","article-title":"Immune responses to influenza virus infection","volume":"162","author":"Kreijtz","year":"2011","journal-title":"Virus Res"},{"key":"2020080404303713100_CIT0003","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJM198307073090103","article-title":"Cytotoxic T-cell immunity to influenza","volume":"309","author":"McMichael","year":"1983","journal-title":"N Engl J Med"},{"key":"2020080404303713100_CIT0004","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/nm.3350","article-title":"Cellular immune correlates of protection against symptomatic pandemic influenza","volume":"19","author":"Sridhar","year":"2013","journal-title":"Nat Med"},{"key":"2020080404303713100_CIT0005","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/icb.2012.54","article-title":"The design and proof of concept for a CD8+ T cell-based vaccine inducing cross-subtype protection against influenza A virus","volume":"91","author":"Tan","year":"2013","journal-title":"Immunol Cell Biol"},{"key":"2020080404303713100_CIT0006","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.coviro.2016.01.016","article-title":"Human influenza viruses and CD8+ T cell responses","volume":"16","author":"Grant","year":"2016","journal-title":"Curr Opin Virol"},{"key":"2020080404303713100_CIT0007","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":"Lee","year":"2008","journal-title":"J Clin Invest"},{"key":"2020080404303713100_CIT0008","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.virusres.2009.05.010","article-title":"Influenza virus morphogenesis and budding","volume":"143","author":"Nayak","year":"2009","journal-title":"Virus Res"},{"key":"2020080404303713100_CIT0009","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1128\/JVI.74.4.1781-1786.2000","article-title":"Role of the influenza virus M1 protein in nuclear export of viral ribonucleoproteins","volume":"74","author":"Bui","year":"2000","journal-title":"J Virol"},{"key":"2020080404303713100_CIT0010","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.copbio.2007.11.002","article-title":"Influenza virus-specific cytotoxic T lymphocytes: a correlate of protection and a basis for vaccine development","volume":"18","author":"Rimmelzwaan","year":"2007","journal-title":"Curr Opin Biotechnol"},{"key":"2020080404303713100_CIT0011","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3390\/vaccines4040033","article-title":"In\ufb02uenza and memory T cells: how to awake the force","volume":"4","author":"Spitaels","year":"2016","journal-title":"Vaccines"},{"key":"2020080404303713100_CIT0012","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/BF01322704","article-title":"Studies on poxvirus infections in irradiated animals","volume":"64","author":"Werner","year":"1980","journal-title":"Arch Virol"},{"key":"2020080404303713100_CIT0013","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.3390\/v6072735","article-title":"Modified vaccinia virus Ankara (MVA) as production platform for vaccines against influenza and other viral respiratory diseases","volume":"6","author":"Altenburg","year":"2014","journal-title":"Viruses"},{"key":"2020080404303713100_CIT0014","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1099\/0022-1317-79-5-1159","article-title":"Modified vaccinia virus Ankara undergoes limited replication in human cells and lacks several immunomodulatory proteins: implications for use as a human vaccine","volume":"79(pt 5)","author":"Blanchard","year":"1998","journal-title":"J Gen Virol"},{"key":"2020080404303713100_CIT0015","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/cid\/ciq015","article-title":"Potent CD8+ T-cell immunogenicity in humans of a novel heterosubtypic influenza A vaccine, MVA-NP+M1","volume":"52","author":"Berthoud","year":"2011","journal-title":"Clin Infect Dis"},{"key":"2020080404303713100_CIT0016","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/cid\/cis327","article-title":"Preliminary assessment of the efficacy of a T-cell-based influenza vaccine, MVA-NP+M1, in humans","volume":"55","author":"Lillie","year":"2012","journal-title":"Clin Infect Dis"},{"key":"2020080404303713100_CIT0017","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.immuni.2014.12.007","article-title":"Tissue-resident memory T cells","volume":"41","author":"Schenkel","year":"2014","journal-title":"Immunity"},{"key":"2020080404303713100_CIT0018","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/ni.1718","article-title":"Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus","volume":"10","author":"Gebhardt","year":"2009","journal-title":"Nat Immunol"},{"key":"2020080404303713100_CIT0019","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nature10851","article-title":"Skin infection generates non-migratory memory CD8+ TRM cells providing global skin immunity","volume":"483","author":"Jiang","year":"2012","journal-title":"Nature"},{"key":"2020080404303713100_CIT0020","doi-asserted-by":"crossref","first-page":"5510","DOI":"10.4049\/jimmunol.1102243","article-title":"Cutting edge: Tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection","volume":"187","author":"Teijaro","year":"2011","journal-title":"J Immunol"},{"key":"2020080404303713100_CIT0021","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nature11522","article-title":"A vaccine strategy that protects against genital herpes by establishing local memory T cells","volume":"491","author":"Shin","year":"2012","journal-title":"Nature"},{"key":"2020080404303713100_CIT0022","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/S0264-410X(99)00183-8","article-title":"Mucosal immune response to trivalent live attenuated intranasal influenza vaccine in children","volume":"18","author":"Boyce","year":"1999","journal-title":"Vaccine"},{"key":"2020080404303713100_CIT0023","doi-asserted-by":"crossref","first-page":"11756","DOI":"10.1128\/JVI.01460-06","article-title":"Cellular immune responses in children and adults receiving inactivated or live attenuated influenza vaccines","volume":"80","author":"He","year":"2006","journal-title":"J Virol"},{"key":"2020080404303713100_CIT0024","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1093\/infdis\/jix165","article-title":"Boosting of cross-reactive and protection-associated T cells in children after live attenuated influenza vaccination","volume":"215","author":"Mohn","year":"2017","journal-title":"J Infect Dis"},{"key":"2020080404303713100_CIT0025","doi-asserted-by":"crossref","first-page":"5014","DOI":"10.4049\/jimmunol.1502632","article-title":"Aerosol delivery of a candidate universal influenza vaccine reduces viral load in pigs challenged with pandemic H1N1 virus","volume":"196","author":"Morgan","year":"2016","journal-title":"J Immunol"},{"key":"2020080404303713100_CIT0026","first-page":"63","article-title":"Immune functions and immunopathology of palatine and nasopharyngeal tonsils.","volume-title":"Immunology of the ear","author":"Brandtzaeg","year":"1987"},{"key":"2020080404303713100_CIT0027","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1046\/j.1365-3083.1997.d01-159.x","article-title":"Nasal lymphoid tissue (NALT) as a mucosal immune inductive site","volume":"46","author":"Wu","year":"1997","journal-title":"Scand J Immunol"},{"key":"2020080404303713100_CIT0028","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.4049\/jimmunol.168.4.1796","article-title":"Nasal-associated lymphoid tissue is a mucosal inductive site for virus-specific humoral and cellular immune responses","volume":"168","author":"Zuercher","year":"2002","journal-title":"J Immunol"},{"key":"2020080404303713100_CIT0029","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 Virol"},{"key":"2020080404303713100_CIT0030","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1016\/j.vaccine.2016.02.028","article-title":"Activation of cross-reactive mucosal T and B cell responses in human nasopharynx-associated lymphoid tissue in vitro by modified vaccinia Ankara-vectored influenza vaccines","volume":"34","author":"Mullin","year":"2016","journal-title":"Vaccine"},{"key":"2020080404303713100_CIT0031","doi-asserted-by":"crossref","first-page":"99","DOI":"10.4236\/ojgen.2014.42013","article-title":"Diversity and frequencies of HLA class I and class II genes of an East African population","volume":"4","author":"Peterson","year":"2014","journal-title":"Open J Genet"},{"key":"2020080404303713100_CIT0032","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":"2020080404303713100_CIT0033","article-title":"Activation and induction of antigen-specific T follicular helper cells play a critical role in live-attenuated influenza vaccine-induced human mucosal anti-influenza antibody response","volume":"92:e00114-18","author":"Aljurayyan","year":"2018","journal-title":"J Virol"},{"key":"2020080404303713100_CIT0034","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/icb.2015.6","article-title":"A large fraction of human tonsillar B cells expressing CD27 are germinal center B cells","volume":"93","author":"Przekopowitz","year":"2015","journal-title":"Immunol Cell Biol"},{"key":"2020080404303713100_CIT0035","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 Infect Dis"},{"key":"2020080404303713100_CIT0036","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.jim.2011.09.008","article-title":"Ex vivo measurement of the cytotoxic capacity of human primary antigen-specific CD8 T cells","volume":"375","author":"Mbitikon-Kobo","year":"2012","journal-title":"J Immunol Methods"},{"key":"2020080404303713100_CIT0037","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/1074-7613(95)90048-9","article-title":"Memory B cells from human tonsils colonize mucosal epithelium and directly present antigen to T cells by rapid up-regulation of B7-1 and B7-2","volume":"2","author":"Liu","year":"1995","journal-title":"Immunity"},{"key":"2020080404303713100_CIT0038","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1146\/annurev.iy.12.040194.004313","article-title":"The CD40 antigen and its ligand","volume":"12","author":"Banchereau","year":"1994","journal-title":"Annu Rev Immunol"},{"key":"2020080404303713100_CIT0039","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1002\/stem.5530120304","article-title":"Molecular control of B lymphocyte growth and differentiation","volume":"12","author":"Banchereau","year":"1994","journal-title":"Stem Cells"},{"key":"2020080404303713100_CIT0040","doi-asserted-by":"crossref","first-page":"8580","DOI":"10.1038\/s41598-017-08719-y","article-title":"Modified vaccinia virus Ankara preferentially targets antigen presenting cells in vitro, ex vivo and in vivo","volume":"7","author":"Altenburg","year":"2017","journal-title":"Sci Rep"},{"key":"2020080404303713100_CIT0041","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/S0042-6822(03)00072-2","article-title":"The immunodominant influenza matrix T cell epitope recognized in human induces influenza protection in HLA-A2\/Kb transgenic mice","volume":"309","author":"Plotnicky","year":"2003","journal-title":"Virology"},{"key":"2020080404303713100_CIT0042","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1172\/JCI44675","article-title":"CD8+ T cells with an intraepithelial phenotype upregulate cytotoxic function upon influenza infection in human lung","volume":"121","author":"Piet","year":"2011","journal-title":"J Clin Invest"},{"key":"2020080404303713100_CIT0043","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/ni.3056","article-title":"Antiviral B cell and T cell immunity in the lungs","volume":"16","author":"Chiu","year":"2014","journal-title":"Nat Immunol"},{"key":"2020080404303713100_CIT0044","doi-asserted-by":"crossref","first-page":"e1005799","DOI":"10.1371\/journal.ppat.1005799","article-title":"Compartmentalization of total and virus-specific tissue-resident memory CD8+ T cells in human lymphoid organs","volume":"12","author":"Woon","year":"2016","journal-title":"PLoS Pathog"},{"key":"2020080404303713100_CIT0045","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3389\/fimmu.2016.00025","article-title":"Balancing immune protection and immune pathology by CD8+ T-cell responses to influenza infection","volume":"7","author":"Duan","year":"2016","journal-title":"Front Immunol"},{"key":"2020080404303713100_CIT0046","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.virol.2012.09.012","article-title":"Anti-viral CD8 T cells and the cytokines that they love","volume":"435","author":"Cox","year":"2013","journal-title":"Virology"},{"key":"2020080404303713100_CIT0047","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nri2274","article-title":"T-cell quality in memory and protection: implications for vaccine design","volume":"8","author":"Seder","year":"2008","journal-title":"Nat Rev Immunol"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiz593\/30966462\/jiz593.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jid\/article-pdf\/222\/5\/807\/33562389\/jiz593.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jid\/article-pdf\/222\/5\/807\/33562389\/jiz593.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T08:32:14Z","timestamp":1596529934000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/222\/5\/807\/5628940"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,19]]},"references-count":47,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,11,19]]},"published-print":{"date-parts":[[2020,8,4]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiz593","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,9,1]]},"published":{"date-parts":[[2019,11,19]]}}}