PMID- 17434154 OWN - NLM STAT- MEDLINE DCOM- 20070727 LR - 20240312 IS - 0008-8749 (Print) IS - 1090-2163 (Electronic) IS - 0008-8749 (Linking) VI - 244 IP - 2 DP - 2006 Dec TI - A systematic bioinformatics approach for selection of epitope-based vaccine targets. PG - 141-7 AB - 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. FAU - Khan, Asif M AU - Khan AM AD - Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597, Singapore. FAU - Miotto, Olivo AU - Miotto O FAU - Heiny, A T AU - Heiny AT FAU - Salmon, Jerome AU - Salmon J FAU - Srinivasan, K N AU - Srinivasan KN FAU - Nascimento, Eduardo J M AU - Nascimento EJ FAU - Marques, Ernesto T A Jr AU - Marques ET Jr FAU - Brusic, Vladimir AU - Brusic V FAU - Tan, Tin Wee AU - Tan TW FAU - August, J Thomas AU - August JT LA - eng GR - U19 AI056541/AI/NIAID NIH HHS/United States GR - U19 AI056541-05/AI/NIAID NIH HHS/United States GR - 5 U19 AI56541/AI/NIAID NIH HHS/United States GR - HHSN2662-00400085C/PHS HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20070416 PL - Netherlands TA - Cell Immunol JT - Cellular immunology JID - 1246405 RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA Antigens) RN - 0 (Viral Nonstructural Proteins) RN - 0 (Viral Vaccines) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Amino Acid Sequence MH - Animals MH - Computational Biology/*methods MH - Conserved Sequence MH - Dengue/*immunology/prevention & control MH - Dengue Virus/genetics/*immunology MH - Epitopes, T-Lymphocyte/genetics/*immunology MH - HLA Antigens/genetics/*immunology MH - Humans MH - Interferon-gamma/immunology MH - Mice MH - Models, Molecular MH - Molecular Sequence Data MH - Sequence Alignment MH - Viral Nonstructural Proteins/genetics/immunology MH - Viral Vaccines/genetics/*immunology PMC - PMC2041846 MID - NIHMS24122 EDAT- 2007/04/17 09:00 MHDA- 2007/07/28 09:00 PMCR- 2007/10/24 CRDT- 2007/04/17 09:00 PHST- 2007/01/31 00:00 [received] PHST- 2007/02/06 00:00 [accepted] PHST- 2007/04/17 09:00 [pubmed] PHST- 2007/07/28 09:00 [medline] PHST- 2007/04/17 09:00 [entrez] PHST- 2007/10/24 00:00 [pmc-release] AID - S0008-8749(07)00026-3 [pii] AID - 10.1016/j.cellimm.2007.02.005 [doi] PST - ppublish SO - Cell Immunol. 2006 Dec;244(2):141-7. doi: 10.1016/j.cellimm.2007.02.005. Epub 2007 Apr 16.