title: Identification of H5N1-specific T-cell responses in a high-risk cohort in vietnam indicates the existence of potential asymptomatic infections.
abstract: BACKGROUND
  Most reported human H5N1 viral infections have been severe and were detected after hospital admission. A case ascertainment bias may therefore exist, with mild cases or asymptomatic infections going undetected. We sought evidence of mild or asymptomatic H5N1 infection by examining H5N1-specific T-cell and antibody responses in a high-risk cohort in Vietnam.
  
  
  METHODS
  Peripheral blood mononuclear cells were tested using interferon-γ enzyme-linked immunospot T assays measuring the response to peptides of influenza H5, H3, and H1 hemagglutinin (HA), N1 and N2 neuraminidase, and the internal proteins of H3N2. Horse erythrocyte hemagglutination inhibition assay was performed to detect antibodies against H5N1.
  
  
  RESULTS
  Twenty-four of 747 individuals demonstrated H5-specific T-cell responses but little or no cross-reactivity with H3 or H1 HA peptides. H5N1 peptide-specific T-cell lines that did not cross-react with H1 or H3 influenza virus HA peptides were generated. Four individuals also had antibodies against H5N1.
  
  
  CONCLUSIONS
  This is the first report of ex vivo H5 HA-specific T-cell responses in a healthy but H5N1-exposed population. Our results indicate that the presence of H5N1-specific T cells could be an additional diagnostic tool for asymptomatic H5N1 infection.
authors.affiliation: MRC Human Immunology Unit, University of Oxford, John Radcliffe Hospital, United Kingdom.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Powell
authors.forename: Annette
authors.initials: A
authors.lastname: Fox
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Peng
authors.forename: Le Thi
authors.initials: le T
authors.lastname: Quynh Mai
authors.forename: Vu T K
authors.initials: VT
authors.lastname: Lien
authors.forename: Nguyen L K
authors.initials: NL
authors.lastname: Hang
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Laurel Y-H
authors.initials: LY
authors.lastname: Lee
authors.forename: Cameron P
authors.initials: CP
authors.lastname: Simmons
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Farrar
authors.forename: Brigitte A
authors.initials: BA
authors.lastname: Askonas
authors.forename: Tran Nhu
authors.initials: TN
authors.lastname: Duong
authors.forename: Pham Quang
authors.initials: PQ
authors.lastname: Thai
authors.forename: Nguyen Thi
authors.initials: NT
authors.lastname: Thu Yen
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland-Jones
authors.forename: Nguyen Tran
authors.initials: NT
authors.lastname: Hien
authors.forename: Peter
authors.initials: P
authors.lastname: Horby
authors.forename: Tao
authors.initials: T
authors.lastname: Dong
mesh_terms: D000914:Antibodies, Viral / Q000097:blood*; D058345:Asymptomatic Infections; D015331:Cohort Studies; D058501:Enzyme-Linked Immunospot Assay; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology; D016036:Seroepidemiologic Studies; D013601:T-Lymphocytes / Q000502:physiology*; D014744:Vietnam / Q000453:epidemiology
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; C109963:hemagglutinin, avian influenza A virus
references.citation: Influenza Other Respir Viruses. 2007 May;1(3):105-12
references.pmid: 19453415
references.citation: Vaccine. 2009 Dec 11;28(2):398-402
references.pmid: 19853073
references.citation: PLoS One. 2009 Nov 20;4(11):e7918
references.pmid: 19936250
references.citation: Nature. 2006 Mar 23;440(7083):435-6
references.pmid: 16554799
references.citation: J Virol. 2008 Jun;82(11):5161-6
references.pmid: 18353950
references.citation: J Virol. 2010 Oct;84(20):10918-22
references.pmid: 20686037
references.citation: Nat Med. 2006 Oct;12(10):1203-7
references.pmid: 16964257
references.citation: Hum Immunol. 2009 Sep;70(9):711-21
references.pmid: 19524006
references.citation: J Immunol. 2005 Jan 1;174(1):449-55
references.pmid: 15611270
references.citation: J Exp Med. 2004 Dec 20;200(12):1547-57
references.pmid: 15596521
references.citation: J Clin Microbiol. 1999 Apr;37(4):937-43
references.pmid: 10074505
references.citation: N Engl J Med. 2005 Sep 29;353(13):1374-85
references.pmid: 16192482
references.citation: J Infect Dis. 1999 Dec;180(6):1763-70
references.pmid: 10558929
references.citation: Vaccine. 2009 Aug 27;27(39):5393-401
references.pmid: 19596415
references.citation: Lancet. 1983 Oct 1;2(8353):762-4
references.pmid: 6137602
references.citation: PLoS One. 2010 May 27;5(5):e10864
references.pmid: 20532246
references.citation: Cell. 2009 Feb 6;136(3):402-10
references.pmid: 19203576
references.citation: Vaccine. 2009 Dec 9;27(52):7359-66
references.pmid: 19800447
references.citation: PLoS One. 2009 Nov 23;4(11):e7948
references.pmid: 19956765
references.citation: Eur J Immunol. 1980 May;10(5):396-401
references.pmid: 6967815
references.citation: Immunology. 2009 Sep;128(1):83-91
references.pmid: 19689738
references.citation: J Infect Dis. 2009 Jun 15;199(12):1744-52
references.pmid: 19416078
references.citation: J Clin Invest. 2008 Oct;118(10):3478-90
references.pmid: 18802496
references.citation: Clin Vaccine Immunol. 2009 Jul;16(7):978-81
references.pmid: 19458206
references.citation: Vaccine. 2010 Feb 3;28(5):1156-67
references.pmid: 20004635
references.citation: Lancet. 2008 Apr 26;371(9622):1464-75
references.pmid: 18440429
references.citation: Epidemiol Infect. 2010 Sep;138(9):1274-80
references.pmid: 20092669
references.citation: Vaccine. 2010 Dec 16;29(2):166-73
references.pmid: 21055500
references.citation: J Med Virol. 1996 Oct;50(2):105-11
references.pmid: 8915874
references.citation: Lancet. 2003 Nov 22;362(9397):1733-45
references.pmid: 14643124
references.citation: J Immunol. 1999 Jun 15;162(12):7578-83
references.pmid: 10358215
references.citation: J Immunol. 2006 May 15;176(10):6333-9
references.pmid: 16670345
references.citation: Vaccine. 2009 Jun 12;27(29):3862-9
references.pmid: 19446935