A systematic bioinformatics approach for selection of epitope-based vaccine targets |
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Authors: | Khan Asif M Miotto Olivo Heiny A T Salmon Jerome Srinivasan K N Nascimento Eduardo J M Marques Ernesto T A Brusic Vladimir Tan Tin Wee August J Thomas |
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Institution: | Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597, Singapore. |
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Abstract: | 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. |
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Keywords: | T-cell epitopes Epitope-based vaccines Bioinformatics Pathogens Immune system Information entropy Conserved sequences Immunological hotspots Altered-ligand effect Supertypes |
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