Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals

被引:367
作者
Lee, Laurel Yong-Hwa [1 ]
Ha, Do Lien Anh [2 ]
Simmons, Cameron [2 ]
de Jong, Menno D. [2 ]
Chau, Nguyen Van Vinh [2 ]
Schumacher, Reto [1 ]
Peng, Yan Chun [1 ]
McMichael, Andrew J. [1 ]
Farrar, Jeremy J. [2 ]
Smith, Geoffrey L. [3 ]
Townsend, Alain R. M. [4 ]
Askonas, Brigitte A. [1 ]
Rowland-Jones, Sarah [1 ]
Dong, Tao [1 ]
机构
[1] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, MRC Human Immunol Unit, Oxford OX3 9DS, England
[2] Univ Oxford, Hosp Trop Dis, Clin Res Unit, Ho Chi Minh City, Vietnam
[3] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Virol, London, England
[4] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Mol Immunol Grp, Oxford OX3 9DS, England
基金
英国医学研究理事会; 英国惠康基金;
关键词
D O I
10.1172/JCI32460
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The threat of avian influenza A (H5N1) infection in humans remains a global health concern. Current influenza vaccines stimulate antibody responses against the surface glycoproteins but are ineffective against strains that have undergone significant antigenic variation. An alternative approach is to stimulate pre-existing memory T cells established by seasonal human influenza A infection that could cross-react with H5N1 by targeting highly conserved internal proteins. To determine how common cross-reactive T cells are, we performed a comprehensive ex vivo analysis of cross-reactive CD4(+) and CD8(+) memory T cell responses to overlapping peptides spanning the full proteome of influenza A/Viet Nam/CL26/2005 (H5N1) and influenza A/New York/232/2004 (H3N2) in healthy individuals from the United Kingdom and Viet Nam. Memory CD4(+) and CD8(+) T cells isolated from the majority of participants exhibited human influenza-specific responses and showed cross-recognition of at least one H5N1 internal protein. Participant CD4(+) and CD8(+) T cells recognized multiple synthesized influenza peptides, including peptides from the H5N1 strain. Matrix protein 1 (M1) and nucleoprotein (NP) were the immunodominant targets of cross-recognition. In addition, cross-reactive CD4(+) and CD8(+) T cells recognized target cells infected with recombinant vaccinia viruses expressing either H5N1 M1 or NP. Thus, vaccine formulas inducing heterosubtypic T cell-mediated immunity may confer broad protection against avian and human influenza A viruses.
引用
收藏
页码:3478 / 3490
页数:13
相关论文
共 75 条
  • [71] CTL epitopes for influenza A including the H5N1 bird flu; genome-, pathogen-, and HLA-wide screening
    Wang, Mingjun
    Lamberth, Kasper
    Harndahl, Mikkel
    Roder, Gustav
    Stryhn, Anette
    Larsen, Mette V.
    Nielsen, Morten
    Lundegaard, Claus
    Tang, Sheila T.
    Dziegiel, Morten H.
    Rosenkvist, Jorgen
    Pedersen, Anders E.
    Buus, Soren
    Claesson, Mogens H.
    Lund, Ole
    [J]. VACCINE, 2007, 25 (15) : 2823 - 2831
  • [72] *WHO, 2007, ANT GEN CHAR H5N1 VI
  • [73] *WHO, 2008, CUM NUMB CONF HUM CA
  • [74] TRANSFER OF SPECIFIC CYTOTOXIC T-LYMPHOCYTES PROTECTS MICE INOCULATED WITH INFLUENZA-VIRUS
    YAP, KL
    ADA, GL
    MCKENZIE, IFC
    [J]. NATURE, 1978, 273 (5659) : 238 - 239
  • [75] INFLUENZA-A VIRUS NUCLEOPROTEIN IS A MAJOR TARGET ANTIGEN FOR CROSS-REACTIVE ANTI-INFLUENZA-A VIRUS CYTO-TOXIC LYMPHOCYTES-T
    YEWDELL, JW
    BENNINK, JR
    SMITH, GL
    MOSS, B
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (06) : 1785 - 1789