A systematic bioinformatics approach for selection of epitope-based vaccine targets.
Epitope-based vaccines provide a new strategy for prophylactic and therapeutic application of pathogen-specific immunity. A critical requirement of this strategy is the identification and selection of T-cell epitopes that act as vaccine targets. This study describes current methodologies for the selection process, with dengue virus as a model system. A combination of publicly available bioinformatics algorithms and computational tools are used to screen and select antigen sequences as potential T-cell epitopes of supertype human leukocyte antigen (HLA) alleles. The selected sequences are tested for biological function by their activation of T-cells of HLA transgenic mice and of pathogen infected subjects. This approach provides an experimental basis for the design of pathogen specific, T-cell epitope-based vaccines that are targeted to majority of the genetic variants of the pathogen, and are effective for a broad range of differences in human leukocyte antigens among the global human population.
Khan
Asif M
AM
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597, Singapore.
Miotto
Olivo
O
Heiny
A T
AT
Salmon
Jerome
J
Srinivasan
K N
KN
Nascimento
Eduardo J M
EJ
Marques
Ernesto T A
ET
Brusic
Vladimir
V
Tan
Tin Wee
TW
August
J Thomas
JT
D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology / Q000379:methods*; D017124:Conserved Sequence; D003715:Dengue / Q000276:immunology* / Q000517:prevention & control; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines; D007371:Interferon-gamma