MersV1, Main, Exploration, bibRecord, 002755

Genotype 1 and global hepatitis C T-cell vaccines designed to optimize coverage of genetic diversity

Identifieur interne : 002755 ( Main/Exploration ); précédent : 002754; suivant : 002756

Genotype 1 and global hepatitis C T-cell vaccines designed to optimize coverage of genetic diversity

Auteurs : Karina Yusim [États-Unis] ; William Fischer [États-Unis] ; Hyejin Yoon [États-Unis] ; James Thurmond [États-Unis] ; Paul W. Fenimore [États-Unis] ; Georg Lauer [États-Unis] ; Bette Korber [États-Unis] ; Carla Kuiken [États-Unis]

Source :

Journal of general virology [ 0022-1317 ] ; 2010.

RBID : Pascal:10-0421927

Descripteurs français

Pascal (Inist)
- Génotype, Lymphocyte T, Vaccin, Diversité génétique, Hépatite virale C.
Wicri :
- topic : Vaccin.

English descriptors

KwdEn :
- Genetic diversity, Genotype, T-Lymphocyte, Vaccine, Viral hepatitis C.

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-Δ). 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.

Affiliations:

Links toward previous steps (curation, corpus...)

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Le document en format XML

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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-Δ). 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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Genotype 1 and global hepatitis C T-cell vaccines designed to optimize coverage of genetic diversity

Genotype 1 and global hepatitis C T-cell vaccines designed to optimize coverage of genetic diversity

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri