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Synthetic Long Peptide Influenza Vaccine Containing Conserved T and B Cell Epitopes Reduces Viral Load in Lungs of Mice and Ferrets

Identifieur interne : 000A59 ( Pmc/Curation ); précédent : 000A58; suivant : 000A60

Synthetic 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 :

RBID : PMC:4457525

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

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PMC:4457525

Le document en format XML

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<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>
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<journal-id journal-id-type="nlm-ta">PLoS One</journal-id>
<journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
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<issn pub-type="epub">1932-6203</issn>
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<publisher-loc>San Francisco, CA USA</publisher-loc>
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<article-id pub-id-type="pmid">26046664</article-id>
<article-id pub-id-type="pmc">4457525</article-id>
<article-id pub-id-type="doi">10.1371/journal.pone.0127969</article-id>
<article-id pub-id-type="publisher-id">PONE-D-15-07531</article-id>
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<subject>Research Article</subject>
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<title-group>
<article-title>Synthetic Long Peptide Influenza Vaccine Containing Conserved T and B Cell Epitopes Reduces Viral Load in Lungs of Mice and Ferrets</article-title>
<alt-title alt-title-type="running-head">Synthetic Long Peptide-Based Influenza Vaccine</alt-title>
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<name>
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<given-names>S. K.</given-names>
</name>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Camps</surname>
<given-names>M. G. M.</given-names>
</name>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Jacobi</surname>
<given-names>R. H. J.</given-names>
</name>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mouthaan</surname>
<given-names>J.</given-names>
</name>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>van Dijken</surname>
<given-names>H.</given-names>
</name>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>van Beek</surname>
<given-names>J.</given-names>
</name>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ossendorp</surname>
<given-names>F.</given-names>
</name>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>de Jonge</surname>
<given-names>J.</given-names>
</name>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="econtrib001">
<sup></sup>
</xref>
<xref rid="cor001" ref-type="corresp">*</xref>
</contrib>
</contrib-group>
<aff id="aff001">
<label>1</label>
<addr-line>Centre for Infectious Disease Control (Cib), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands</addr-line>
</aff>
<aff id="aff002">
<label>2</label>
<addr-line>Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Leiden, the Netherlands</addr-line>
</aff>
<contrib-group>
<contrib contrib-type="editor">
<name>
<surname>Kang</surname>
<given-names>Sang-Moo</given-names>
</name>
<role>Academic Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">
<addr-line>Georgia State University, UNITED STATES</addr-line>
</aff>
<author-notes>
<fn fn-type="COI-statement" id="coi001">
<p>
<bold>Competing Interests: </bold>
The authors have declared that no competing interests exist.</p>
</fn>
<fn fn-type="con" id="contrib001">
<p>Conceived and designed the experiments: SRH MC FO JvB JdJ. Performed the experiments: SRH MC RJ JM HvD JdJ. Analyzed the data: SRH JdJ. Contributed reagents/materials/analysis tools: MC FO. Wrote the paper: SRH FO JvB JdJ.</p>
</fn>
<fn fn-type="other" id="econtrib001">
<p>‡ These authors are shared senior authors on this work.</p>
</fn>
<corresp id="cor001">* E-mail:
<email>Jorgen.de.Jonge@rivm.nl</email>
</corresp>
</author-notes>
<pub-date pub-type="epub">
<day>5</day>
<month>6</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="collection">
<year>2015</year>
</pub-date>
<volume>10</volume>
<issue>6</issue>
<elocation-id>e0127969</elocation-id>
<history>
<date date-type="received">
<day>19</day>
<month>2</month>
<year>2015</year>
</date>
<date date-type="accepted">
<day>22</day>
<month>4</month>
<year>2015</year>
</date>
</history>
<permissions>
<copyright-statement>© 2015 Rosendahl Huber et al</copyright-statement>
<copyright-year>2015</copyright-year>
<copyright-holder>Rosendahl Huber et al</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:type="simple" xlink:href="pone.0127969.pdf"></self-uri>
<abstract>
<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>
</abstract>
<funding-group>
<funding-statement>Funding provided to FO, JvB, JdJ by the European Union Seventh Framework Programme under grant number 201169, Identification of Mechanisms Correlating with Susceptibility for Avian Influenza (IMECS),
<ext-link ext-link-type="uri" xlink:href="http://ec.europa.eu/research/health/infectious-diseases/emerging-epidemics/projects/175_en.html">http://ec.europa.eu/research/health/infectious-diseases/emerging-epidemics/projects/175_en.html</ext-link>
. Funding provided to JdJ, HvD, JM by the Health Program of the European Union under grant number 2009 1106, Fast Vaccination (FASTVAC),
<ext-link ext-link-type="uri" xlink:href="http://www.fastvac.eu/work-packages/liaison-for-vaccine-deployment">http://www.fastvac.eu/work-packages/liaison-for-vaccine-deployment</ext-link>
. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement>
</funding-group>
<counts>
<fig-count count="6"></fig-count>
<table-count count="2"></table-count>
<page-count count="19"></page-count>
</counts>
<custom-meta-group>
<custom-meta id="data-availability">
<meta-name>Data Availability</meta-name>
<meta-value>All relevant data are within the paper and its Supporting Information files.</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
<notes>
<title>Data Availability</title>
<p>All relevant data are within the paper and its Supporting Information files.</p>
</notes>
</front>
</pmc>
</record>

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