Genotype 1 and global hepatitis C T-cell vaccines designed to optimize coverage of genetic diversity.
Identifieur interne : 002631 ( Main/Exploration ); précédent : 002630; suivant : 002632Genotype 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
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 001F72
- to stream PubMed, to step Curation: 001F72
- to stream PubMed, to step Checkpoint: 001E40
- to stream Ncbi, to step Merge: 000729
- to stream Ncbi, to step Curation: 000729
- to stream Ncbi, to step Checkpoint: 000729
- to stream Main, to step Merge: 002656
- to stream Main, to step Curation: 002631
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Genotype 1 and global hepatitis C T-cell vaccines designed to optimize coverage of genetic diversity.</title><author><name sortKey="Yusim, Karina" sort="Yusim, Karina" uniqKey="Yusim K" first="Karina" last="Yusim">Karina Yusim</name><affiliation wicri:level="2"><nlm:affiliation>Los Alamos National Laboratory, Theory Division, Los Alamos, NM 87545, USA. kyusim@lanl.gov</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Los Alamos National Laboratory, Theory Division, Los Alamos, NM 87545</wicri:regionArea><placeName><region type="state">Nouveau-Mexique</region></placeName></affiliation></author><author><name sortKey="Fischer, William" sort="Fischer, William" uniqKey="Fischer W" first="William" last="Fischer">William Fischer</name></author><author><name sortKey="Yoon, Hyejin" sort="Yoon, Hyejin" uniqKey="Yoon H" first="Hyejin" last="Yoon">Hyejin Yoon</name></author><author><name sortKey="Thurmond, James" sort="Thurmond, James" uniqKey="Thurmond J" first="James" last="Thurmond">James Thurmond</name></author><author><name sortKey="Fenimore, Paul W" sort="Fenimore, Paul W" uniqKey="Fenimore P" first="Paul W" last="Fenimore">Paul W. Fenimore</name></author><author><name sortKey="Lauer, Georg" sort="Lauer, Georg" uniqKey="Lauer G" first="Georg" last="Lauer">Georg Lauer</name></author><author><name sortKey="Korber, Bette" sort="Korber, Bette" uniqKey="Korber B" first="Bette" last="Korber">Bette Korber</name></author><author><name sortKey="Kuiken, Carla" sort="Kuiken, Carla" uniqKey="Kuiken C" first="Carla" last="Kuiken">Carla Kuiken</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2010">2010</date><idno type="RBID">pubmed:20053820</idno><idno type="pmid">20053820</idno><idno type="doi">10.1099/vir.0.017491-0</idno><idno type="wicri:Area/PubMed/Corpus">001F72</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001F72</idno><idno type="wicri:Area/PubMed/Curation">001F72</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001F72</idno><idno type="wicri:Area/PubMed/Checkpoint">001E40</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001E40</idno><idno type="wicri:Area/Ncbi/Merge">000729</idno><idno type="wicri:Area/Ncbi/Curation">000729</idno><idno type="wicri:Area/Ncbi/Checkpoint">000729</idno><idno type="wicri:Area/Main/Merge">002656</idno><idno type="wicri:Area/Main/Curation">002631</idno><idno type="wicri:Area/Main/Exploration">002631</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Genotype 1 and global hepatitis C T-cell vaccines designed to optimize coverage of genetic diversity.</title><author><name sortKey="Yusim, Karina" sort="Yusim, Karina" uniqKey="Yusim K" first="Karina" last="Yusim">Karina Yusim</name><affiliation wicri:level="2"><nlm:affiliation>Los Alamos National Laboratory, Theory Division, Los Alamos, NM 87545, USA. kyusim@lanl.gov</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Los Alamos National Laboratory, Theory Division, Los Alamos, NM 87545</wicri:regionArea><placeName><region type="state">Nouveau-Mexique</region></placeName></affiliation></author><author><name sortKey="Fischer, William" sort="Fischer, William" uniqKey="Fischer W" first="William" last="Fischer">William Fischer</name></author><author><name sortKey="Yoon, Hyejin" sort="Yoon, Hyejin" uniqKey="Yoon H" first="Hyejin" last="Yoon">Hyejin Yoon</name></author><author><name sortKey="Thurmond, James" sort="Thurmond, James" uniqKey="Thurmond J" first="James" last="Thurmond">James Thurmond</name></author><author><name sortKey="Fenimore, Paul W" sort="Fenimore, Paul W" uniqKey="Fenimore P" first="Paul W" last="Fenimore">Paul W. Fenimore</name></author><author><name sortKey="Lauer, Georg" sort="Lauer, Georg" uniqKey="Lauer G" first="Georg" last="Lauer">Georg Lauer</name></author><author><name sortKey="Korber, Bette" sort="Korber, Bette" uniqKey="Korber B" first="Bette" last="Korber">Bette Korber</name></author><author><name sortKey="Kuiken, Carla" sort="Kuiken, Carla" uniqKey="Kuiken C" first="Carla" last="Kuiken">Carla Kuiken</name></author></analytic><series><title level="j">The Journal of general virology</title><idno type="eISSN">1465-2099</idno><imprint><date when="2010" type="published">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Epitopes, T-Lymphocyte (genetics)</term><term>Epitopes, T-Lymphocyte (immunology)</term><term>Genetic Variation</term><term>Genotype</term><term>Hepacivirus (genetics)</term><term>Hepacivirus (immunology)</term><term>Hepatitis C (immunology)</term><term>Hepatitis C (prevention & control)</term><term>Humans</term><term>Recombinant Proteins (genetics)</term><term>Recombinant Proteins (immunology)</term><term>T-Lymphocytes (immunology)</term><term>Vaccines, Synthetic (genetics)</term><term>Vaccines, Synthetic (immunology)</term><term>Viral Hepatitis Vaccines (immunology)</term><term>Viral Nonstructural Proteins (genetics)</term><term>Viral Nonstructural Proteins (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Déterminants antigéniques des lymphocytes T (génétique)</term><term>Déterminants antigéniques des lymphocytes T (immunologie)</term><term>Génotype</term><term>Hepacivirus (génétique)</term><term>Hepacivirus (immunologie)</term><term>Humains</term><term>Hépatite C ()</term><term>Hépatite C (immunologie)</term><term>Lymphocytes T (immunologie)</term><term>Protéines recombinantes (génétique)</term><term>Protéines recombinantes (immunologie)</term><term>Protéines virales non structurales (génétique)</term><term>Protéines virales non structurales (immunologie)</term><term>Vaccins contre les hépatites virales (immunologie)</term><term>Vaccins synthétiques (génétique)</term><term>Vaccins synthétiques (immunologie)</term><term>Variation génétique</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Epitopes, T-Lymphocyte</term><term>Recombinant Proteins</term><term>Vaccines, Synthetic</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Epitopes, T-Lymphocyte</term><term>Recombinant Proteins</term><term>Vaccines, Synthetic</term><term>Viral Hepatitis Vaccines</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Hepacivirus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Déterminants antigéniques des lymphocytes T</term><term>Hepacivirus</term><term>Protéines recombinantes</term><term>Protéines virales non structurales</term><term>Vaccins synthétiques</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Déterminants antigéniques des lymphocytes T</term><term>Hepacivirus</term><term>Hépatite C</term><term>Lymphocytes T</term><term>Protéines recombinantes</term><term>Protéines virales non structurales</term><term>Vaccins contre les hépatites virales</term><term>Vaccins synthétiques</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Hepacivirus</term><term>Hepatitis C</term><term>T-Lymphocytes</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Hepatitis C</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Genetic Variation</term><term>Genotype</term><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Génotype</term><term>Humains</term><term>Hépatite C</term><term>Variation génétique</term></keywords></textClass></profileDesc></teiHeader><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></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Nouveau-Mexique</li></region></list><tree><noCountry><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></noCountry><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></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002631 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 002631 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:20053820
|texte= Genotype 1 and global hepatitis C T-cell vaccines designed to optimize coverage of genetic diversity.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:20053820" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a MersV1
| This area was generated with Dilib version V0.6.33. |  |