MersV1, PascalFrancis, Checkpoint, bibRecord, 000065

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

Identifieur interne : 000065 ( PascalFrancis/Checkpoint ); précédent : 000064; suivant : 000066

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:

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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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<fC07 i1="01" i2="X" l="ENG"><s0>Digestive diseases</s0>
<s5>13</s5>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Aparato digestivo patología</s0>
<s5>13</s5>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Virose</s0>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Viral disease</s0>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Virosis</s0>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Infection</s0>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Infection</s0>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Infección</s0>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Pathologie du foie</s0>
<s5>16</s5>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Hepatic disease</s0>
<s5>16</s5>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Hígado patología</s0>
<s5>16</s5>
</fC07>
<fN21><s1>277</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Massachusetts</li>
<li>Nouveau-Mexique</li>
</region>
</list>
<tree><country name="États-Unis"><region name="Nouveau-Mexique"><name sortKey="Yusim, Karina" sort="Yusim, Karina" uniqKey="Yusim K" first="Karina" last="Yusim">Karina Yusim</name>
</region>
<name sortKey="Fenimore, Paul W" sort="Fenimore, Paul W" uniqKey="Fenimore P" first="Paul W." last="Fenimore">Paul W. Fenimore</name>
<name sortKey="Fischer, William" sort="Fischer, William" uniqKey="Fischer W" first="William" last="Fischer">William Fischer</name>
<name sortKey="Korber, Bette" sort="Korber, Bette" uniqKey="Korber B" first="Bette" last="Korber">Bette Korber</name>
<name sortKey="Kuiken, Carla" sort="Kuiken, Carla" uniqKey="Kuiken C" first="Carla" last="Kuiken">Carla Kuiken</name>
<name sortKey="Lauer, Georg" sort="Lauer, Georg" uniqKey="Lauer G" first="Georg" last="Lauer">Georg Lauer</name>
<name sortKey="Thurmond, James" sort="Thurmond, James" uniqKey="Thurmond J" first="James" last="Thurmond">James Thurmond</name>
<name sortKey="Yoon, Hyejin" sort="Yoon, Hyejin" uniqKey="Yoon H" first="Hyejin" last="Yoon">Hyejin Yoon</name>
</country>
</tree>
</affiliations>
</record>

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