From genome to vaccine: in silico predictions, ex vivo verification
Identifieur interne : 003558 ( Main/Exploration ); précédent : 003557; suivant : 003559From genome to vaccine: in silico predictions, ex vivo verification
Auteurs : Anne S. De Groot [États-Unis] ; Andrew Bosma [États-Unis] ; Natasha Chinai [États-Unis] ; Julie Frost [États-Unis] ; Bill M. Jesdale [États-Unis] ; Michael A. Gonzalez [États-Unis] ; William Martin [États-Unis] ; Caitlin Saint-Aubin [États-Unis]Source :
- Vaccine [ 0264-410X ] ; 2001.
Descripteurs français
- Wicri :
- topic : Vaccin.
English descriptors
- KwdEn :
- Teeft :
- Algorithm, Allele, Amino, Amino acid, Amino acids, Assay, Bind, Binder, Binding assay, Binding motifs, Binding peptides, Binding probability, Bioinformatics, Bioinformatics tools, Blastimer, Candidate epitopes, Cell epitopes, Cell response, Clade, Conservatrix, Cytotoxic, Database, Elispot, Elispot assays, Elispot response, Epimatrix, Epimer, Epitope, Epitope mapping, Genome, Genome scan, Groot, Human retroviruses, Immune, Immune response, Immune system, Immunol, Ligand, Matrix, Mycobacterium, Mycobacterium tuberculosis, Neural networks, Open reading frames, Orfs, Patent blast, Pathogen, Peptide, Promiscuous, Promiscuous epitopes, Protein sequences, Public databases, Research laboratory, Sequence database, Study subjects, Supertype, Supertype family, Vaccine, Vaccine design, Vaccine development.
Abstract
Abstract: Bioinformatics tools enable researchers to move rapidly from genome sequence to vaccine design. EpiMer and EpiMatrix are computer-driven pattern-matching algorithms that identify T cell epitopes. Conservatrix, BlastiMer, and Patent-Blast permit the analysis of protein sequences for highly conserved regions, for homology with other known proteins, and for homology with previously patented epitopes, respectively. Two applications of these tools to epitope-driven vaccine design are described in this review. Using Conservatrix and EpiMatrix, we analyzed more than 10 000 HIV-1 sequences and identified peptides that were potentially immunostimulatory and highly conserved across HIV-1 clades. MHC binding assays and CTL assays have been carried out: 50 (69%) of the 72 candidate epitopes bound in assays with cell lines expressing the corresponding MHC molecule; 15 of the 24 B7 peptides (63%) stimulated gamma-interferon release in ELISpot assays. These results lend support to the bioinformatics approach to selecting novel, conserved, HIV-1 CTL epitopes. EpiMatrix was also applied to the entire ‘proteome’ derived from two Mycobacterium tuberculosis (Mtb) genomes. Using EpiMatrix, BlastiMer, and Patent-Blast, we narrowed the list of putative Mtb epitopes to be tested in vitro from 1 600 000 to 3000, a 99.8% reduction. The pace of vaccine design will accelerate when these and other bioinformatics tools are systematically applied to whole genomes and used in combination with in vitro methods for screening and confirming epitopes.
Url:
DOI: 10.1016/S0264-410X(01)00145-1
Affiliations:
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EpiMer and EpiMatrix are computer-driven pattern-matching algorithms that identify T cell epitopes. Conservatrix, BlastiMer, and Patent-Blast permit the analysis of protein sequences for highly conserved regions, for homology with other known proteins, and for homology with previously patented epitopes, respectively. Two applications of these tools to epitope-driven vaccine design are described in this review. Using Conservatrix and EpiMatrix, we analyzed more than 10 000 HIV-1 sequences and identified peptides that were potentially immunostimulatory and highly conserved across HIV-1 clades. MHC binding assays and CTL assays have been carried out: 50 (69%) of the 72 candidate epitopes bound in assays with cell lines expressing the corresponding MHC molecule; 15 of the 24 B7 peptides (63%) stimulated gamma-interferon release in ELISpot assays. These results lend support to the bioinformatics approach to selecting novel, conserved, HIV-1 CTL epitopes. EpiMatrix was also applied to the entire ‘proteome’ derived from two Mycobacterium tuberculosis (Mtb) genomes. Using EpiMatrix, BlastiMer, and Patent-Blast, we narrowed the list of putative Mtb epitopes to be tested in vitro from 1 600 000 to 3000, a 99.8% reduction. The pace of vaccine design will accelerate when these and other bioinformatics tools are systematically applied to whole genomes and used in combination with in vitro methods for screening and confirming epitopes.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Rhode Island</li></region><settlement><li>Providence (Rhode Island)</li></settlement><orgName><li>Université Brown</li></orgName></list><tree><country name="États-Unis"><noRegion><name sortKey="De Groot, Anne S" sort="De Groot, Anne S" uniqKey="De Groot A" first="Anne S." last="De Groot">Anne S. De Groot</name></noRegion><name sortKey="Bosma, Andrew" sort="Bosma, Andrew" uniqKey="Bosma A" first="Andrew" last="Bosma">Andrew Bosma</name><name sortKey="Chinai, Natasha" sort="Chinai, Natasha" uniqKey="Chinai N" first="Natasha" last="Chinai">Natasha Chinai</name><name sortKey="De Groot, Anne S" sort="De Groot, Anne S" uniqKey="De Groot A" first="Anne S." last="De Groot">Anne S. De Groot</name><name sortKey="Frost, Julie" sort="Frost, Julie" uniqKey="Frost J" first="Julie" last="Frost">Julie Frost</name><name sortKey="Gonzalez, Michael A" sort="Gonzalez, Michael A" uniqKey="Gonzalez M" first="Michael A." last="Gonzalez">Michael A. Gonzalez</name><name sortKey="Jesdale, Bill M" sort="Jesdale, Bill M" uniqKey="Jesdale B" first="Bill M." last="Jesdale">Bill M. Jesdale</name><name sortKey="Martin, William" sort="Martin, William" uniqKey="Martin W" first="William" last="Martin">William Martin</name><name sortKey="Saint Aubin, Caitlin" sort="Saint Aubin, Caitlin" uniqKey="Saint Aubin C" first="Caitlin" last="Saint-Aubin">Caitlin Saint-Aubin</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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