Synthetic Long Peptide Influenza Vaccine Containing Conserved T and B Cell Epitopes Reduces Viral Load in Lungs of Mice and Ferrets
Identifieur interne : 000512 ( Main/Exploration ); précédent : 000511; suivant : 000513Synthetic Long Peptide Influenza Vaccine Containing Conserved T and B Cell Epitopes Reduces Viral Load in Lungs of Mice and Ferrets
Auteurs : S. K. Rosendahl Huber [Pays-Bas] ; M. G. M. Camps [Pays-Bas] ; R. H. J. Jacobi [Pays-Bas] ; J. Mouthaan [Pays-Bas] ; H. Van Dijken [Pays-Bas] ; J. Van Beek [Pays-Bas] ; F. Ossendorp [Pays-Bas] ; J. De Jonge [Pays-Bas]Source :
- PLoS ONE [ 1932-6203 ] ; 2015.
Abstract
Currently licensed influenza vaccines mainly induce antibodies against highly variable epitopes. Due to antigenic drift, protection is subtype or strain-specific and regular vaccine updates are required. In case of antigenic shifts, which have caused several pandemics in the past, completely new vaccines need to be developed. We set out to develop a vaccine that provides protection against a broad range of influenza viruses. Therefore, highly conserved parts of the influenza A virus (IAV) were selected of which we constructed antibody and T cell inducing peptide-based vaccines. The B epitope vaccine consists of the highly conserved HA2 fusion peptide and M2e peptide coupled to a CD4 helper epitope. The T epitope vaccine comprises 25 overlapping synthetic long peptides of 26-34 amino acids, thereby avoiding restriction for a certain MHC haplotype. These peptides are derived from nucleoprotein (NP), polymerase basic protein 1 (PB1) and matrix protein 1 (M1). C57BL/6 mice, BALB/c mice, and ferrets were vaccinated with the B epitopes, 25 SLP or a combination of both. Vaccine-specific antibodies were detected in sera of mice and ferrets and vaccine-specific cellular responses were measured in mice. Following challenge, both mice and ferrets showed a reduction of virus titers in the lungs in response to vaccination. Summarizing, a peptide-based vaccine directed against conserved parts of influenza virus containing B and T cell epitopes shows promising results for further development. Such a vaccine may reduce disease burden and virus transmission during pandemic outbreaks.
Url:
DOI: 10.1371/journal.pone.0127969
PubMed: 26046664
PubMed Central: 4457525
Affiliations:
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K." last="Rosendahl Huber">S. K. Rosendahl Huber</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Centre for Infectious Disease Control (Cib), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands</addr-line></nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Centre for Infectious Disease Control (Cib), National Institute for Public Health and the Environment (RIVM), Bilthoven</wicri:regionArea><wicri:noRegion>Bilthoven</wicri:noRegion></affiliation></author><author><name sortKey="Camps, M G M" sort="Camps, M G M" uniqKey="Camps M" first="M. G. M." last="Camps">M. G. M. Camps</name><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Leiden, the Netherlands</addr-line></nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Jacobi, R H J" sort="Jacobi, R H J" uniqKey="Jacobi R" first="R. H. J." last="Jacobi">R. H. J. 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Van Dijken</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Centre for Infectious Disease Control (Cib), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands</addr-line></nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Centre for Infectious Disease Control (Cib), National Institute for Public Health and the Environment (RIVM), Bilthoven</wicri:regionArea><wicri:noRegion>Bilthoven</wicri:noRegion></affiliation></author><author><name sortKey="Van Beek, J" sort="Van Beek, J" uniqKey="Van Beek J" first="J." last="Van Beek">J. Van Beek</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Centre for Infectious Disease Control (Cib), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands</addr-line></nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Centre for Infectious Disease Control (Cib), National Institute for Public Health and the Environment (RIVM), Bilthoven</wicri:regionArea><wicri:noRegion>Bilthoven</wicri:noRegion></affiliation></author><author><name sortKey="Ossendorp, F" sort="Ossendorp, F" uniqKey="Ossendorp F" first="F." last="Ossendorp">F. Ossendorp</name><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Leiden, the Netherlands</addr-line></nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="De Jonge, J" sort="De Jonge, J" uniqKey="De Jonge J" first="J." last="De Jonge">J. De Jonge</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Centre for Infectious Disease Control (Cib), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands</addr-line></nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Centre for Infectious Disease Control (Cib), National Institute for Public Health and the Environment (RIVM), Bilthoven</wicri:regionArea><wicri:noRegion>Bilthoven</wicri:noRegion></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Currently licensed influenza vaccines mainly induce antibodies against highly variable epitopes. Due to antigenic drift, protection is subtype or strain-specific and regular vaccine updates are required. In case of antigenic shifts, which have caused several pandemics in the past, completely new vaccines need to be developed. We set out to develop a vaccine that provides protection against a broad range of influenza viruses. Therefore, highly conserved parts of the influenza A virus (IAV) were selected of which we constructed antibody and T cell inducing peptide-based vaccines. The B epitope vaccine consists of the highly conserved HA2 fusion peptide and M2e peptide coupled to a CD4 helper epitope. The T epitope vaccine comprises 25 overlapping synthetic long peptides of 26-34 amino acids, thereby avoiding restriction for a certain MHC haplotype. These peptides are derived from nucleoprotein (NP), polymerase basic protein 1 (PB1) and matrix protein 1 (M1). C57BL/6 mice, BALB/c mice, and ferrets were vaccinated with the B epitopes, 25 SLP or a combination of both. Vaccine-specific antibodies were detected in sera of mice and ferrets and vaccine-specific cellular responses were measured in mice. Following challenge, both mice and ferrets showed a reduction of virus titers in the lungs in response to vaccination. Summarizing, a peptide-based vaccine directed against conserved parts of influenza virus containing B and T cell epitopes shows promising results for further development. Such a vaccine may reduce disease burden and virus transmission during pandemic outbreaks.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Plotkin, Sa" uniqKey="Plotkin S">SA Plotkin</name></author><author><name sortKey="Orenstein, Wa" uniqKey="Orenstein W">WA Orenstein</name></author><author><name sortKey="Offit, Pa" uniqKey="Offit P">PA Offit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Quinones Parra, S" uniqKey="Quinones Parra S">S Quinones-Parra</name></author><author><name sortKey="Loh, L" uniqKey="Loh L">L Loh</name></author><author><name sortKey="Brown, Le" uniqKey="Brown L">LE Brown</name></author><author><name sortKey="Kedzierska, K" uniqKey="Kedzierska K">K Kedzierska</name></author><author><name sortKey="Valkenburg, Sa" uniqKey="Valkenburg S">SA Valkenburg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chun, S" uniqKey="Chun S">S 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uniqKey="Rosendahl Huber S" first="S. K." last="Rosendahl Huber">S. K. Rosendahl Huber</name></noRegion><name sortKey="Camps, M G M" sort="Camps, M G M" uniqKey="Camps M" first="M. G. M." last="Camps">M. G. M. Camps</name><name sortKey="De Jonge, J" sort="De Jonge, J" uniqKey="De Jonge J" first="J." last="De Jonge">J. De Jonge</name><name sortKey="Jacobi, R H J" sort="Jacobi, R H J" uniqKey="Jacobi R" first="R. H. J." last="Jacobi">R. H. J. Jacobi</name><name sortKey="Mouthaan, J" sort="Mouthaan, J" uniqKey="Mouthaan J" first="J." last="Mouthaan">J. Mouthaan</name><name sortKey="Ossendorp, F" sort="Ossendorp, F" uniqKey="Ossendorp F" first="F." last="Ossendorp">F. Ossendorp</name><name sortKey="Van Beek, J" sort="Van Beek, J" uniqKey="Van Beek J" first="J." last="Van Beek">J. Van Beek</name><name sortKey="Van Dijken, H" sort="Van Dijken, H" uniqKey="Van Dijken H" first="H." last="Van Dijken">H. Van Dijken</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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