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

Khan AM, Miotto O, Heiny AT, Salmon J, Srinivasan KN, Nascimento EJ, Marques ET, Brusic V, Tan TW, August JT.
Cell Immunol. 2006 Dec;244(2):141-147. Epub 2007 Apr 16.
PUBMED PMID: 17434154
Out link: Full-text
Impact Factor Year 2009: 2.698
No. of Citations: 15 (total): 9 (non-self) & 6 (self)

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.

This article has been cited by other articles:

1) Heiny AT, Miotto O, Srinivasan KN, Khan AM, Zhang GL, Brusic V, Tan TW, August JT. Evolutionarily conserved protein sequences of influenza a viruses, avian and human, as vaccine targets. PLoS ONE. 2007 Nov 21;2(11):e1190. PMID: 18030326

2) Miotto O, Heiny A, Tan TW, August JT, Brusic V. Identification of human-to-human transmissibility factors in PB2 proteins of influenza A by large-scale mutual information analysis. BMC Bioinformatics. 2008;9 Suppl 1:S18. PMID: 18315849

3) Miotto O, Tan TW, Brusic V. Rule-based knowledge aggregation for large-scale protein sequence analysis of influenza A viruses. BMC Bioinformatics. 2008;9 Suppl 1:S7. PMID: 18315860

4) Sidney J, Peters B, Frahm N, Brander C, Sette A. HLA class I supertypes: a revised and updated classification. BMC Immunol. 2008 Jan 22;9:1. PMID: 18211710

5) Koo QY, Khan AM, Jung KO, Ramdas S, Miotto O, Tan TW, Brusic V, Salmon J, August JT. Conservation and variability of West Nile virus proteins. PLoS One. 2009;4(4):e5352. Epub 2009 Apr 29. PMID: 19401763

6)
De Groot AS, McMurry J, Moise L. Prediction of immunogenicity: in silico paradigms, ex vivo and in vivo correlates. Curr Opin Pharmacol. 2008 Oct;8(5):620-6. Epub 2008 Sep 19. Review.
PMID: 18775515

7) Khan AM, Miotto O, Nascimento EJ, Srinivasan KN, Heiny AT, Zhang GL, Marques ET, Tan TW, Brusic V, Salmon J, August JT. Conservation and variability of dengue virus proteins: implications for vaccine design. PLoS Negl Trop Dis. 2008 Aug 13;2(8):e272. PMID: 18698358

8) Yauch LE, Zellweger RM, Kotturi MF, Qutubuddin A, Sidney J, Peters B, Prestwood TR, Sette A, Shresta S. A protective role for dengue virus-specific CD8+ T cells. J Immunol. 2009 Apr 15;182(8):4865-73. PMID: 19342665


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