Genotype 1 and global hepatitis C T-cell vaccines designed to optimize coverage of genetic diversity
Identifieur interne : 000064 ( PascalFrancis/Corpus ); précédent : 000063; suivant : 000065Genotype 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 KuikenSource :
- Journal of general virology [ 0022-1317 ] ; 2010.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
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.
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Format Inist (serveur)
NO : | PASCAL 10-0421927 INIST |
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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 |
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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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<s5>16</s5>
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<s5>16</s5>
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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>
<FD>Génotype; Lymphocyte T; Vaccin; Diversité génétique; Hépatite virale C</FD>
<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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