Epitope specific T-cell responses against influenza A in a healthy population.
Pre-existing human CD4(+) and CD8(+) T-cell-mediated immunity may be a useful correlate of protection against severe influenza disease. Identification and evaluation of common epitopes recognized by T cells with broad cross-reactivity is therefore important to guide universal influenza vaccine development, and to monitor immunological preparedness against pandemics. We have retrieved an optimal combination of MHC class I and class II restricted epitopes from the Immune Epitope Database (www.iedb.org), by defining a fitness score function depending on prevalence, sequence conservancy and HLA super-type coverage. Optimized libraries of CD4(+) and CD8(+) T-cell epitopes were selected from influenza antigens commonly present in seasonal and pandemic influenza strains from 1934 to 2009. These epitope pools were used to characterize human T-cell responses in healthy donors using interferon-γ ELISPOT assays. Upon stimulation, significant CD4(+) and CD8(+) T-cell responses were induced, primarily recognizing epitopes from the conserved viral core proteins. Furthermore, the CD4(+) and CD8(+) T cells were phenotypically characterized regarding functionality, cytotoxic potential and memory phenotype using flow cytometry. Optimized sets of T-cell peptide epitopes may be a useful tool to monitor the efficacy of clinical trials, the immune status of a population to predict immunological preparedness against pandemics, as well as being candidates for universal influenza vaccines.
Department of Bacteriology and Immunology, Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway.|K. G. Jebsen Centre for Influenza Vaccine Research, Oslo University Hospital, Oslo, Norway.
Miloje
http://orcid.org/0000-0002-7376-4568
M
Savic
Department of Bacteriology and Immunology, Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway.|K. G. Jebsen Centre for Influenza Vaccine Research, Oslo University Hospital, Oslo, Norway.
Jennifer L
JL
Dembinski
La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
Yohan
Y
Kim
Department of Bacteriology and Immunology, Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway.|K. G. Jebsen Centre for Influenza Vaccine Research, Oslo University Hospital, Oslo, Norway.
Gro
G
Tunheim
K. G. Jebsen Centre for Influenza Vaccine Research, Oslo University Hospital, Oslo, Norway.|The Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.
Rebecca J
RJ
Cox
Department of Bacteriology and Immunology, Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway.|K. G. Jebsen Centre for Influenza Vaccine Research, Oslo University Hospital, Oslo, Norway.
Fredrik
F
Oftung
La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
Bjoern
B
Peters
Department of Bacteriology and Immunology, Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway.|K. G. Jebsen Centre for Influenza Vaccine Research, Oslo University Hospital, Oslo, Norway.
Siri
S
Mjaaland
D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D019295:Computational Biology; D030562:Databases, Protein; D015195:Drug Design; D058501:Enzyme-Linked Immunospot Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D009980:Influenza A virus / Q000187:drug effects / Q000276:immunology* / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000276:immunology* / Q000627:therapeutic use; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D059425:Interferon-gamma Release Tests; D008213:Lymphocyte Activation; D019151:Peptide Library; D010641:Phenotype
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; C573415:IFNG protein, human; D007252:Influenza Vaccines; D019151:Peptide Library; D007371:Interferon-gamma
T-cell epitopes; biomarkers; cross-reactivity; influenza A virus; vaccine