Genotype 1 and global hepatitis C T-cell vaccines designed to optimize coverage of genetic diversity.
Identifieur interne : 001F72 ( PubMed/Corpus ); précédent : 001F71; suivant : 001F73Genotype 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 :
- The Journal of general virology [ 1465-2099 ] ; 2010.
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
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pubmed:20053820Le document en format XML
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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></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><nlm:affiliation>Los Alamos National Laboratory, Theory Division, Los Alamos, NM 87545, USA. kyusim@lanl.gov</nlm:affiliation></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="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="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></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><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">20053820</PMID><DateCompleted><Year>2010</Year><Month>04</Month><Day>30</Day></DateCompleted><DateRevised><Year>2010</Year><Month>04</Month><Day>16</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1465-2099</ISSN><JournalIssue CitedMedium="Internet"><Volume>91</Volume><Issue>Pt 5</Issue><PubDate><Year>2010</Year><Month>May</Month></PubDate></JournalIssue><Title>The Journal of general virology</Title><ISOAbbreviation>J. Gen. Virol.</ISOAbbreviation></Journal><ArticleTitle>Genotype 1 and global hepatitis C T-cell vaccines designed to optimize coverage of genetic diversity.</ArticleTitle><Pagination><MedlinePgn>1194-206</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1099/vir.0.017491-0</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Yusim</LastName><ForeName>Karina</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Los Alamos National Laboratory, Theory Division, Los Alamos, NM 87545, USA. kyusim@lanl.gov</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fischer</LastName><ForeName>William</ForeName><Initials>W</Initials></Author><Author ValidYN="Y"><LastName>Yoon</LastName><ForeName>Hyejin</ForeName><Initials>H</Initials></Author><Author ValidYN="Y"><LastName>Thurmond</LastName><ForeName>James</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Fenimore</LastName><ForeName>Paul W</ForeName><Initials>PW</Initials></Author><Author ValidYN="Y"><LastName>Lauer</LastName><ForeName>Georg</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Korber</LastName><ForeName>Bette</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Kuiken</LastName><ForeName>Carla</ForeName><Initials>C</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2010</Year><Month>01</Month><Day>06</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>J Gen Virol</MedlineTA><NlmUniqueID>0077340</NlmUniqueID><ISSNLinking>0022-1317</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018984">Epitopes, 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