MersV1, PascalFrancis, Corpus, bibRecord, 000064

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

Identifieur interne : 000064 ( PascalFrancis/Corpus ); précédent : 000063; suivant : 000065

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

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

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.

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.

Notice en format standard (ISO 2709)

Pour connaître la documentation sur le format Inist Standard.

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A08	`01`	`1`	`ENG`	`@1 Genotype 1 and global hepatitis C T-cell vaccines designed to optimize coverage of genetic diversity`
A11	`01`	`1`		`@1 YUSIM (Karina)`
A11	`02`	`1`		`@1 FISCHER (William)`
A11	`03`	`1`		`@1 YOON (Hyejin)`
A11	`04`	`1`		`@1 THURMOND (James)`
A11	`05`	`1`		`@1 FENIMORE (Paul W.)`
A11	`06`	`1`		`@1 LAUER (Georg)`
A11	`07`	`1`		`@1 KORBER (Bette)`
A11	`08`	`1`		`@1 KUIKEN (Carla)`
A14	`01`			`@1 Los Alamos National Laboratory, Theory Division @2 Los Alamos, NM 87545 @3 USA @Z 1 aut. @Z 2 aut. @Z 3 aut. @Z 4 aut. @Z 5 aut. @Z 7 aut. @Z 8 aut.`
A14	`02`			`@1 Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School @2 Boston, MA 02114 @3 USA @Z 6 aut.`
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A23	`01`			`@0 ENG`
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A44				`@0 0000 @1 © 2010 INIST-CNRS. All rights reserved.`
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A47	`01`	`1`		`@0 10-0421927`
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A64	`01`	`1`		`@0 Journal of general virology`
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C01	`01`		`ENG`	@0 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.
C02	`01`	`X`		`@0 002A05C10`
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C03	`01`	`X`	`FRE`	`@0 Génotype @5 05`
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C03	`01`	`X`	`SPA`	`@0 Genotipo @5 05`
C03	`02`	`X`	`FRE`	`@0 Lymphocyte T @5 06`
C03	`02`	`X`	`ENG`	`@0 T-Lymphocyte @5 06`
C03	`02`	`X`	`SPA`	`@0 Linfocito T @5 06`
C03	`03`	`X`	`FRE`	`@0 Vaccin @5 07`
C03	`03`	`X`	`ENG`	`@0 Vaccine @5 07`
C03	`03`	`X`	`SPA`	`@0 Vacuna @5 07`
C03	`04`	`X`	`FRE`	`@0 Diversité génétique @5 08`
C03	`04`	`X`	`ENG`	`@0 Genetic diversity @5 08`
C03	`04`	`X`	`SPA`	`@0 Diversidad genética @5 08`
C03	`05`	`X`	`FRE`	`@0 Hépatite virale C @5 14`
C03	`05`	`X`	`ENG`	`@0 Viral hepatitis C @5 14`
C03	`05`	`X`	`SPA`	`@0 Hepatítis virica C @5 14`
C07	`01`	`X`	`FRE`	`@0 Pathologie de l'appareil digestif @5 13`
C07	`01`	`X`	`ENG`	`@0 Digestive diseases @5 13`
C07	`01`	`X`	`SPA`	`@0 Aparato digestivo patología @5 13`
C07	`02`	`X`	`FRE`	`@0 Virose`
C07	`02`	`X`	`ENG`	`@0 Viral disease`
C07	`02`	`X`	`SPA`	`@0 Virosis`
C07	`03`	`X`	`FRE`	`@0 Infection`
C07	`03`	`X`	`ENG`	`@0 Infection`
C07	`03`	`X`	`SPA`	`@0 Infección`
C07	`04`	`X`	`FRE`	`@0 Pathologie du foie @5 16`
C07	`04`	`X`	`ENG`	`@0 Hepatic disease @5 16`
C07	`04`	`X`	`SPA`	`@0 Hígado patología @5 16`
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N44	`01`			`@1 OTO`
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Format Inist (serveur)

NO :	PASCAL 10-0421927 INIST
ET :	Genotype 1 and global hepatitis C T-cell vaccines designed to optimize coverage of genetic diversity
AU :	YUSIM (Karina); FISCHER (William); YOON (Hyejin); THURMOND (James); FENIMORE (Paul W.); LAUER (Georg); KORBER (Bette); KUIKEN (Carla)
AF :	Los Alamos National Laboratory, Theory Division/Los Alamos, NM 87545/Etats-Unis (1 aut., 2 aut., 3 aut., 4 aut., 5 aut., 7 aut., 8 aut.); Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School/Boston, MA 02114/Etats-Unis (6 aut.)
DT :	Publication en série; Niveau analytique
SO :	Journal of general virology; ISSN 0022-1317; Coden JGVIAY; Royaume-Uni; Da. 2010; Vol. 91; No. p. 5; Pp. 1194-1206; Bibl. 1 p.3/4
LA :	Anglais
EA :	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.
CC :	002A05C10; 002A05C07
FD :	Génotype; Lymphocyte T; Vaccin; Diversité génétique; Hépatite virale C
FG :	Pathologie de l'appareil digestif; Virose; Infection; Pathologie du foie
ED :	Genotype; T-Lymphocyte; Vaccine; Genetic diversity; Viral hepatitis C
EG :	Digestive diseases; Viral disease; Infection; Hepatic disease
SD :	Genotipo; Linfocito T; Vacuna; Diversidad genética; Hepatítis virica C
LO :	INIST-13533.354000181111700120
ID :	10-0421927

Links to Exploration step

Pascal:10-0421927

Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Genotype 1 and global hepatitis C T-cell vaccines designed to optimize coverage of genetic diversity</title>
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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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<fC01 i1="01" l="ENG"><s0>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.</s0>
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<server><NO>PASCAL 10-0421927 INIST</NO>
<ET>Genotype 1 and global hepatitis C T-cell vaccines designed to optimize coverage of genetic diversity</ET>
<AU>YUSIM (Karina); FISCHER (William); YOON (Hyejin); THURMOND (James); FENIMORE (Paul W.); LAUER (Georg); KORBER (Bette); KUIKEN (Carla)</AU>
<AF>Los Alamos National Laboratory, Theory Division/Los Alamos, NM 87545/Etats-Unis (1 aut., 2 aut., 3 aut., 4 aut., 5 aut., 7 aut., 8 aut.); Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School/Boston, MA 02114/Etats-Unis (6 aut.)</AF>
<DT>Publication en série; Niveau analytique</DT>
<SO>Journal of general virology; ISSN 0022-1317; Coden JGVIAY; Royaume-Uni; Da. 2010; Vol. 91; No. p. 5; Pp. 1194-1206; Bibl. 1 p.3/4</SO>
<LA>Anglais</LA>
<EA>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.</EA>
<CC>002A05C10; 002A05C07</CC>
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<FG>Pathologie de l'appareil digestif; Virose; Infection; Pathologie du foie</FG>
<ED>Genotype; T-Lymphocyte; Vaccine; Genetic diversity; Viral hepatitis C</ED>
<EG>Digestive diseases; Viral disease; Infection; Hepatic disease</EG>
<SD>Genotipo; Linfocito T; Vacuna; Diversidad genética; Hepatítis virica C</SD>
<LO>INIST-13533.354000181111700120</LO>
<ID>10-0421927</ID>
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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

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