TY - JOUR

T1 - CTL epitopes for influenza A including the H5N1 bird flu; genome-, pathogen-, and HLA-wide screening.

AU - Wang, Mingjun

AU - Lamberth, Kasper

AU - Harndahl, Mikkel

AU - Røder, Gustav

AU - Stryhn, Anette

AU - Larsen, Mette V

AU - Nielsen, Morten

AU - Lundegaard, Claus

AU - Tang, Sheila T

AU - Dziegiel, Morten H

AU - Rosenkvist, Jørgen

AU - Pedersen, Anders E

AU - Buus, Søren

AU - Claesson, Mogens H

AU - Lund, Ole

N1 - Keywords: Adult; Aged; Animals; Birds; Epitopes, T-Lymphocyte; Female; Genetic Screening; Genome, Viral; HLA-A Antigens; HLA-B Antigens; Humans; Influenza A Virus, H5N1 Subtype; Influenza A virus; Influenza in Birds; Influenza, Human; Male; Membrane Transport Proteins; Middle Aged; Proteasome Endopeptidase Complex; T-Lymphocytes, Cytotoxic

PY - 2006

Y1 - 2006

N2 - The purpose of the present study is to perform a global screening for new immunogenic HLA class I (HLA-I) restricted cytotoxic T cell (CTL) epitopes of potential utility as candidates of influenza A-virus diagnostics and vaccines. We used predictions of antigen processing and presentation, the latter encompassing 12 different HLA class I supertypes with >99% population coverage, and searched for conserved epitopes from available influenza A viral protein sequences. Peptides corresponding to 167 predicted peptide-HLA-I interactions were synthesized, tested for peptide-HLA-I interactions in a biochemical assay and for influenza-specific, HLA-I-restricted CTL responses in an IFN-gamma ELISPOT assay. Eighty-nine peptides could be confirmed as HLA-I binders, and 13 could be confirmed as CTL targets. The 13 epitopes, are highly conserved among human influenza A pathogens, and all of these epitopes are present in the emerging bird flu isolates. Our study demonstrates that present technology enables a fast global screening for T cell immune epitopes of potential diagnostics and vaccine interest. This technology includes immuno-bioinformatics predictors with the capacity to perform fast genome-, pathogen-, and HLA-wide searches for immune targets. To exploit this new potential, a coordinated international effort to analyze the precious source of information represented by rare patients, such as the current victims of bird flu, would be essential.

AB - The purpose of the present study is to perform a global screening for new immunogenic HLA class I (HLA-I) restricted cytotoxic T cell (CTL) epitopes of potential utility as candidates of influenza A-virus diagnostics and vaccines. We used predictions of antigen processing and presentation, the latter encompassing 12 different HLA class I supertypes with >99% population coverage, and searched for conserved epitopes from available influenza A viral protein sequences. Peptides corresponding to 167 predicted peptide-HLA-I interactions were synthesized, tested for peptide-HLA-I interactions in a biochemical assay and for influenza-specific, HLA-I-restricted CTL responses in an IFN-gamma ELISPOT assay. Eighty-nine peptides could be confirmed as HLA-I binders, and 13 could be confirmed as CTL targets. The 13 epitopes, are highly conserved among human influenza A pathogens, and all of these epitopes are present in the emerging bird flu isolates. Our study demonstrates that present technology enables a fast global screening for T cell immune epitopes of potential diagnostics and vaccine interest. This technology includes immuno-bioinformatics predictors with the capacity to perform fast genome-, pathogen-, and HLA-wide searches for immune targets. To exploit this new potential, a coordinated international effort to analyze the precious source of information represented by rare patients, such as the current victims of bird flu, would be essential.

U2 - 10.1016/j.vaccine.2006.12.038

DO - 10.1016/j.vaccine.2006.12.038

M3 - Journal article

C2 - 17254671

VL - 25

SP - 2823

EP - 2831

JO - Vaccine

JF - Vaccine

SN - 0264-410X

IS - 15

ER -