Genotype 1 and global hepatitis C T-cell vaccines designed to optimize coverage of genetic diversity.
Identifieur interne : 001F72 ( PubMed/Curation ); précédent : 001F71; suivant : 001F73Genotype 1 and global hepatitis C T-cell vaccines designed to optimize coverage of genetic diversity.
Auteurs : Karina Yusim [États-Unis] ; William Fischer ; Hyejin Yoon ; James Thurmond ; Paul W. Fenimore ; Georg Lauer ; Bette Korber ; Carla KuikenSource :
- The Journal of general virology [ 1465-2099 ] ; 2010.
Descripteurs français
- KwdFr :
- Déterminants antigéniques des lymphocytes T (génétique), Déterminants antigéniques des lymphocytes T (immunologie), Génotype, Hepacivirus (génétique), Hepacivirus (immunologie), Humains, Hépatite C (), Hépatite C (immunologie), Lymphocytes T (immunologie), Protéines recombinantes (génétique), Protéines recombinantes (immunologie), Protéines virales non structurales (génétique), Protéines virales non structurales (immunologie), Vaccins contre les hépatites virales (immunologie), Vaccins synthétiques (génétique), Vaccins synthétiques (immunologie), Variation génétique.
- MESH :
- génétique : Déterminants antigéniques des lymphocytes T, Hepacivirus, Protéines recombinantes, Protéines virales non structurales, Vaccins synthétiques.
- immunologie : Déterminants antigéniques des lymphocytes T, Hepacivirus, Hépatite C, Lymphocytes T, Protéines recombinantes, Protéines virales non structurales, Vaccins contre les hépatites virales, Vaccins synthétiques.
- Génotype, Humains, Hépatite C, Variation génétique.
English descriptors
- KwdEn :
- Epitopes, T-Lymphocyte (genetics), Epitopes, T-Lymphocyte (immunology), Genetic Variation, Genotype, Hepacivirus (genetics), Hepacivirus (immunology), Hepatitis C (immunology), Hepatitis C (prevention & control), Humans, Recombinant Proteins (genetics), Recombinant Proteins (immunology), T-Lymphocytes (immunology), Vaccines, Synthetic (genetics), Vaccines, Synthetic (immunology), Viral Hepatitis Vaccines (immunology), Viral Nonstructural Proteins (genetics), Viral Nonstructural Proteins (immunology).
- MESH :
- chemical , genetics : Epitopes, T-Lymphocyte, Recombinant Proteins, Vaccines, Synthetic, Viral Nonstructural Proteins.
- chemical , immunology : Epitopes, T-Lymphocyte, Recombinant Proteins, Vaccines, Synthetic, Viral Hepatitis Vaccines, Viral Nonstructural Proteins.
- genetics : Hepacivirus.
- immunology : Hepacivirus, Hepatitis C, T-Lymphocytes.
- prevention & control : Hepatitis C.
- Genetic Variation, Genotype, Humans.
Abstract
Immunological control of hepatitis C virus (HCV) is possible and is probably mediated by host T-cell responses, but the genetic diversity of the virus poses a major challenge to vaccine development. We considered monovalent and polyvalent candidates for an HCV vaccine, including natural, consensus and synthetic 'mosaic' sequence cocktails. Mosaic vaccine reagents were designed using a computational approach first applied to and demonstrated experimentally for human immunodeficiency virus type 1 (HIV-Delta). Mosaic proteins resemble natural proteins, but are assembled from fragments of natural sequences via a genetic algorithm and optimized to maximize the coverage of potential T-cell epitopes (all 9-mers) found in natural sequences and to minimize the inclusion of rare 9-mers to avoid vaccine-specific responses. Genotype 1-specific and global vaccine cocktails were evaluated. Among vaccine candidates considered, polyvalent mosaic sequences provided the best coverage of both known and potential epitopes and had the fewest rare epitopes. A global vaccine based on conserved proteins across genotypes may be feasible, as a five-antigen mosaic cocktail provided 90, 77 and 70% coverage of the Core, NS3 and NS4 proteins, respectively; protein coverage diminished with increased protein variability, dropping to 38% for NS2. For the genotype 1-specific vaccine, the H77 prototype vaccine sequence matched only 50% of the potential epitopes in the population, whilst a polyprotein three-antigen mosaic cocktail increased potential epitope coverage to 83%. More than 75% coverage of all HCV proteins was achieved with a three-antigen mosaic cocktail, suggesting that genotype-specific vaccines could also include the more variable proteins.
DOI: 10.1099/vir.0.017491-0
PubMed: 20053820
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<front><div type="abstract" xml:lang="en">Immunological control of hepatitis C virus (HCV) is possible and is probably mediated by host T-cell responses, but the genetic diversity of the virus poses a major challenge to vaccine development. We considered monovalent and polyvalent candidates for an HCV vaccine, including natural, consensus and synthetic 'mosaic' sequence cocktails. Mosaic vaccine reagents were designed using a computational approach first applied to and demonstrated experimentally for human immunodeficiency virus type 1 (HIV-Delta). Mosaic proteins resemble natural proteins, but are assembled from fragments of natural sequences via a genetic algorithm and optimized to maximize the coverage of potential T-cell epitopes (all 9-mers) found in natural sequences and to minimize the inclusion of rare 9-mers to avoid vaccine-specific responses. Genotype 1-specific and global vaccine cocktails were evaluated. Among vaccine candidates considered, polyvalent mosaic sequences provided the best coverage of both known and potential epitopes and had the fewest rare epitopes. A global vaccine based on conserved proteins across genotypes may be feasible, as a five-antigen mosaic cocktail provided 90, 77 and 70% coverage of the Core, NS3 and NS4 proteins, respectively; protein coverage diminished with increased protein variability, dropping to 38% for NS2. For the genotype 1-specific vaccine, the H77 prototype vaccine sequence matched only 50% of the potential epitopes in the population, whilst a polyprotein three-antigen mosaic cocktail increased potential epitope coverage to 83%. More than 75% coverage of all HCV proteins was achieved with a three-antigen mosaic cocktail, suggesting that genotype-specific vaccines could also include the more variable proteins.</div>
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<Abstract><AbstractText>Immunological control of hepatitis C virus (HCV) is possible and is probably mediated by host T-cell responses, but the genetic diversity of the virus poses a major challenge to vaccine development. We considered monovalent and polyvalent candidates for an HCV vaccine, including natural, consensus and synthetic 'mosaic' sequence cocktails. Mosaic vaccine reagents were designed using a computational approach first applied to and demonstrated experimentally for human immunodeficiency virus type 1 (HIV-Delta). Mosaic proteins resemble natural proteins, but are assembled from fragments of natural sequences via a genetic algorithm and optimized to maximize the coverage of potential T-cell epitopes (all 9-mers) found in natural sequences and to minimize the inclusion of rare 9-mers to avoid vaccine-specific responses. Genotype 1-specific and global vaccine cocktails were evaluated. Among vaccine candidates considered, polyvalent mosaic sequences provided the best coverage of both known and potential epitopes and had the fewest rare epitopes. A global vaccine based on conserved proteins across genotypes may be feasible, as a five-antigen mosaic cocktail provided 90, 77 and 70% coverage of the Core, NS3 and NS4 proteins, respectively; protein coverage diminished with increased protein variability, dropping to 38% for NS2. For the genotype 1-specific vaccine, the H77 prototype vaccine sequence matched only 50% of the potential epitopes in the population, whilst a polyprotein three-antigen mosaic cocktail increased potential epitope coverage to 83%. More than 75% coverage of all HCV proteins was achieved with a three-antigen mosaic cocktail, suggesting that genotype-specific vaccines could also include the more variable proteins.</AbstractText>
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