A systematic bioinformatics approach for selection of epitope-based vaccine targets


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KHAN M. A. , Miotto O., Heiny A. T. , Salmon J., Srinivasan K. N. , Nascimento E. J. M. , ...More

CELLULAR IMMUNOLOGY, vol.244, no.2, pp.141-147, 2006 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 244 Issue: 2
  • Publication Date: 2006
  • Doi Number: 10.1016/j.cellimm.2007.02.005
  • Title of Journal : CELLULAR IMMUNOLOGY
  • Page Numbers: pp.141-147
  • Keywords: T-cell epitopes, epitope-based vaccines, bioinformatics, pathogens, immune systems, information entropy, conserved sequences, immunological hotspots, altered-ligand effect, supertypes, T-CELL EPITOPES, MHC CLASS-I, HIV ENVELOPE, DENGUE, RESPONSES, IDENTIFICATION, PREDICTION, PROTEIN, CLUSTERS, BINDING

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. (c) 2007 Elsevier Inc. All rights reserved.