OVX836 a recombinant nucleoprotein vaccine inducing cellular responses and protective efficacy against multiple influenza A subtypes
Identifieur interne : 000042 ( Pmc/Checkpoint ); précédent : 000041; suivant : 000043OVX836 a recombinant nucleoprotein vaccine inducing cellular responses and protective efficacy against multiple influenza A subtypes
Auteurs : Judith Del Campo [France] ; Andres Pizzorno ; Sophia Djebali [France] ; Julien Bouley [France] ; Marjorie Haller [France] ; Jimena Pérez-Vargas [France] ; Bruno Lina [France] ; Guy Boivin [Canada] ; Marie-Eve Hamelin [Canada] ; Florence Nicolas [France] ; Alexandre Le Vert [France] ; Yann Leverrier [France] ; Manuel Rosa-Calatrava ; Jacqueline Marvel [France] ; Fergal Hill [France]Source :
- NPJ Vaccines [ 2059-0105 ] ; 2019.
Abstract
Inactivated influenza vaccines (IIVs) lack broad efficacy. Cellular immunity to a conserved internal antigen, the nucleoprotein (NP), has been correlated to protection against pandemic and seasonal influenza and thus could have the potential to broaden vaccine efficacy. We developed OVX836, a recombinant protein vaccine based on an oligomerized NP, which shows increased uptake by dendritic cells and immunogenicity compared with NP. Intramuscular immunization in mice with OVX836 induced strong NP-specific CD4+ and CD8+ T-cell systemic responses and established CD8+ tissue memory T cells in the lung parenchyma. Strikingly, OVX836 protected mice against viral challenge with three different influenza A subtypes, isolated several decades apart and induced a reduction in viral load. When co-administered with IIV, OVX836 was even more effective in reducing lung viral load.
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DOI: 10.1038/s41541-019-0098-4
PubMed: 30701093
PubMed Central: 6344521
Affiliations:
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Université de Lyon,</institution></institution-wrap>Lyon, F- 69008 France</nlm:aff><wicri:noCountry code="subfield">F- 69008 France</wicri:noCountry></affiliation></author><author><name sortKey="Marvel, Jacqueline" sort="Marvel, Jacqueline" uniqKey="Marvel J" first="Jacqueline" last="Marvel">Jacqueline Marvel</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0450 6033</institution-id><institution-id institution-id-type="GRID">grid.462394.e</institution-id><institution>Immunity and Cytotoxic Lymphocytes,</institution><institution>Centre International de Recherche en Infectiologie, INSERM, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon. 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Université de Lyon,</institution></institution-wrap>Lyon, F- 69008 France</nlm:aff><wicri:noCountry code="subfield">F- 69008 France</wicri:noCountry></affiliation></author><author><name sortKey="Djebali, Sophia" sort="Djebali, Sophia" uniqKey="Djebali S" first="Sophia" last="Djebali">Sophia Djebali</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0450 6033</institution-id><institution-id institution-id-type="GRID">grid.462394.e</institution-id><institution>Immunity and Cytotoxic Lymphocytes,</institution><institution>Centre International de Recherche en Infectiologie, INSERM, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon. Université de Lyon,</institution></institution-wrap>F-69007 Lyon, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>F-69007 Lyon</wicri:regionArea></affiliation></author><author><name sortKey="Bouley, Julien" sort="Bouley, Julien" uniqKey="Bouley J" first="Julien" last="Bouley">Julien Bouley</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Osivax, 99, rue de Gerland, 69007 Lyon, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Osivax, 99, rue de Gerland, 69007 Lyon</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Haller, Marjorie" sort="Haller, Marjorie" uniqKey="Haller M" first="Marjorie" last="Haller">Marjorie Haller</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Osivax, 99, rue de Gerland, 69007 Lyon, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Osivax, 99, rue de Gerland, 69007 Lyon</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Perez Vargas, Jimena" sort="Perez Vargas, Jimena" uniqKey="Perez Vargas J" first="Jimena" last="Pérez-Vargas">Jimena Pérez-Vargas</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Osivax, 99, rue de Gerland, 69007 Lyon, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Osivax, 99, rue de Gerland, 69007 Lyon</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2172 4233</institution-id><institution-id institution-id-type="GRID">grid.25697.3f</institution-id><institution>Present Address: Enveloped Viruses, Vectors and Immunotherapy Team, Centre International de Recherché en Infectiologie (CIRI), INSERM U1111,</institution><institution>Université de Lyon,</institution></institution-wrap>Lyon, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Lyon</wicri:regionArea></affiliation></author><author><name sortKey="Lina, Bruno" sort="Lina, Bruno" uniqKey="Lina B" first="Bruno" last="Lina">Bruno Lina</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0450 6033</institution-id><institution-id institution-id-type="GRID">grid.462394.e</institution-id><institution>Virologie et Pathologie Humaine - VirPath Team,</institution><institution>Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, École Normale Supérieure de Lyon, Université Claude Bernard Lyon 1. Université de Lyon,</institution></institution-wrap>Lyon, F- 69008 France</nlm:aff><wicri:noCountry code="subfield">F- 69008 France</wicri:noCountry></affiliation><affiliation wicri:level="3"><nlm:aff id="Aff4">Hospices Civils de Lyon, Centre National de Référence des Virus Influenza France Sud, Laboratoire de Virologie, Groupement Hospitalier Nord, Lyon, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Hospices Civils de Lyon, Centre National de Référence des Virus Influenza France Sud, Laboratoire de Virologie, Groupement Hospitalier Nord, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Boivin, Guy" sort="Boivin, Guy" uniqKey="Boivin G" first="Guy" last="Boivin">Guy Boivin</name><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 8390</institution-id><institution-id institution-id-type="GRID">grid.23856.3a</institution-id><institution>Centre de Recherche en Infectiologie of the Centre Hospitalier Universitaire de Québec and Université Laval,</institution></institution-wrap>Québec, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Québec</wicri:regionArea></affiliation></author><author><name sortKey="Hamelin, Marie Eve" sort="Hamelin, Marie Eve" uniqKey="Hamelin M" first="Marie-Eve" last="Hamelin">Marie-Eve Hamelin</name><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 8390</institution-id><institution-id institution-id-type="GRID">grid.23856.3a</institution-id><institution>Centre de Recherche en Infectiologie of the Centre Hospitalier Universitaire de Québec and Université Laval,</institution></institution-wrap>Québec, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Québec</wicri:regionArea></affiliation></author><author><name sortKey="Nicolas, Florence" sort="Nicolas, Florence" uniqKey="Nicolas F" first="Florence" last="Nicolas">Florence Nicolas</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Osivax, 99, rue de Gerland, 69007 Lyon, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Osivax, 99, rue de Gerland, 69007 Lyon</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Le Vert, Alexandre" sort="Le Vert, Alexandre" uniqKey="Le Vert A" first="Alexandre" last="Le Vert">Alexandre Le Vert</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Osivax, 99, rue de Gerland, 69007 Lyon, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Osivax, 99, rue de Gerland, 69007 Lyon</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Leverrier, Yann" sort="Leverrier, Yann" uniqKey="Leverrier Y" first="Yann" last="Leverrier">Yann Leverrier</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0450 6033</institution-id><institution-id institution-id-type="GRID">grid.462394.e</institution-id><institution>Immunity and Cytotoxic Lymphocytes,</institution><institution>Centre International de Recherche en Infectiologie, INSERM, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon. Université de Lyon,</institution></institution-wrap>F-69007 Lyon, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>F-69007 Lyon</wicri:regionArea></affiliation></author><author><name sortKey="Rosa Calatrava, Manuel" sort="Rosa Calatrava, Manuel" uniqKey="Rosa Calatrava M" first="Manuel" last="Rosa-Calatrava">Manuel Rosa-Calatrava</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0450 6033</institution-id><institution-id institution-id-type="GRID">grid.462394.e</institution-id><institution>Virologie et Pathologie Humaine - VirPath Team,</institution><institution>Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, École Normale Supérieure de Lyon, Université Claude Bernard Lyon 1. Université de Lyon,</institution></institution-wrap>Lyon, F- 69008 France</nlm:aff><wicri:noCountry code="subfield">F- 69008 France</wicri:noCountry></affiliation></author><author><name sortKey="Marvel, Jacqueline" sort="Marvel, Jacqueline" uniqKey="Marvel J" first="Jacqueline" last="Marvel">Jacqueline Marvel</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0450 6033</institution-id><institution-id institution-id-type="GRID">grid.462394.e</institution-id><institution>Immunity and Cytotoxic Lymphocytes,</institution><institution>Centre International de Recherche en Infectiologie, INSERM, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon. Université de Lyon,</institution></institution-wrap>F-69007 Lyon, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>F-69007 Lyon</wicri:regionArea></affiliation></author><author><name sortKey="Hill, Fergal" sort="Hill, Fergal" uniqKey="Hill F" first="Fergal" last="Hill">Fergal Hill</name><affiliation wicri:level="3"><nlm:aff id="Aff1">Osivax, 99, rue de Gerland, 69007 Lyon, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Osivax, 99, rue de Gerland, 69007 Lyon</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author></analytic><series><title level="j">NPJ Vaccines</title><idno type="eISSN">2059-0105</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">Inactivated influenza vaccines (IIVs) lack broad efficacy. Cellular immunity to a conserved internal antigen, the nucleoprotein (NP), has been correlated to protection against pandemic and seasonal influenza and thus could have the potential to broaden vaccine efficacy. We developed OVX836, a recombinant protein vaccine based on an oligomerized NP, which shows increased uptake by dendritic cells and immunogenicity compared with NP. Intramuscular immunization in mice with OVX836 induced strong NP-specific CD4+ and CD8+ T-cell systemic responses and established CD8+ tissue memory T cells in the lung parenchyma. Strikingly, OVX836 protected mice against viral challenge with three different influenza A subtypes, isolated several decades apart and induced a reduction in viral load. When co-administered with IIV, OVX836 was even more effective in reducing lung viral load.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Belongia, Ea" uniqKey="Belongia E">EA Belongia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xie, H" uniqKey="Xie H">H Xie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Flannery, B" uniqKey="Flannery B">B Flannery</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chambers, Bs" uniqKey="Chambers B">BS Chambers</name></author><author><name sortKey="Parkhouse, K" uniqKey="Parkhouse K">K Parkhouse</name></author><author><name sortKey="Ross, Tm" uniqKey="Ross T">TM Ross</name></author><author><name sortKey="Alby, K" uniqKey="Alby K">K Alby</name></author><author><name sortKey="Hensley, Se" uniqKey="Hensley S">SE 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<front><journal-meta><journal-id journal-id-type="nlm-ta">NPJ Vaccines</journal-id><journal-id journal-id-type="iso-abbrev">NPJ Vaccines</journal-id><journal-title-group><journal-title>NPJ Vaccines</journal-title></journal-title-group><issn pub-type="epub">2059-0105</issn><publisher><publisher-name>Nature Publishing Group UK</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">30701093</article-id><article-id pub-id-type="pmc">6344521</article-id><article-id pub-id-type="publisher-id">98</article-id><article-id pub-id-type="doi">10.1038/s41541-019-0098-4</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>OVX836 a recombinant nucleoprotein vaccine inducing cellular responses and protective efficacy against multiple influenza A subtypes</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Del Campo</surname><given-names>Judith</given-names></name><address><email>jdelcampo@osivax.com</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-0918-6804</contrib-id><name><surname>Pizzorno</surname><given-names>Andres</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-0567-5387</contrib-id><name><surname>Djebali</surname><given-names>Sophia</given-names></name><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Bouley</surname><given-names>Julien</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Haller</surname><given-names>Marjorie</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Pérez-Vargas</surname><given-names>Jimena</given-names></name><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Lina</surname><given-names>Bruno</given-names></name><xref ref-type="aff" rid="Aff2">2</xref><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Boivin</surname><given-names>Guy</given-names></name><xref ref-type="aff" rid="Aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Hamelin</surname><given-names>Marie-Eve</given-names></name><xref ref-type="aff" rid="Aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Nicolas</surname><given-names>Florence</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Le Vert</surname><given-names>Alexandre</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-4227-5446</contrib-id><name><surname>Leverrier</surname><given-names>Yann</given-names></name><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Rosa-Calatrava</surname><given-names>Manuel</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0001-6241-459X</contrib-id><name><surname>Marvel</surname><given-names>Jacqueline</given-names></name><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Hill</surname><given-names>Fergal</given-names></name><address><email>fhill@osivax.com</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><aff id="Aff1"><label>1</label>Osivax, 99, rue de Gerland, 69007 Lyon, France</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0450 6033</institution-id><institution-id institution-id-type="GRID">grid.462394.e</institution-id><institution>Virologie et Pathologie Humaine - VirPath Team,</institution><institution>Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, École Normale Supérieure de Lyon, Université Claude Bernard Lyon 1. Université de Lyon,</institution></institution-wrap>Lyon, F- 69008 France</aff><aff id="Aff3"><label>3</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0450 6033</institution-id><institution-id institution-id-type="GRID">grid.462394.e</institution-id><institution>Immunity and Cytotoxic Lymphocytes,</institution><institution>Centre International de Recherche en Infectiologie, INSERM, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon. Université de Lyon,</institution></institution-wrap>F-69007 Lyon, France</aff><aff id="Aff4"><label>4</label>Hospices Civils de Lyon, Centre National de Référence des Virus Influenza France Sud, Laboratoire de Virologie, Groupement Hospitalier Nord, Lyon, France</aff><aff id="Aff5"><label>5</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 8390</institution-id><institution-id institution-id-type="GRID">grid.23856.3a</institution-id><institution>Centre de Recherche en Infectiologie of the Centre Hospitalier Universitaire de Québec and Université Laval,</institution></institution-wrap>Québec, Canada</aff><aff id="Aff6"><label>6</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2172 4233</institution-id><institution-id institution-id-type="GRID">grid.25697.3f</institution-id><institution>Present Address: Enveloped Viruses, Vectors and Immunotherapy Team, Centre International de Recherché en Infectiologie (CIRI), INSERM U1111,</institution><institution>Université de Lyon,</institution></institution-wrap>Lyon, France</aff></contrib-group><pub-date pub-type="epub"><day>23</day><month>1</month><year>2019</year></pub-date><pub-date pub-type="pmc-release"><day>23</day><month>1</month><year>2019</year></pub-date><pub-date pub-type="collection"><year>2019</year></pub-date><volume>4</volume><elocation-id>4</elocation-id><history><date date-type="received"><day>27</day><month>3</month><year>2018</year></date><date date-type="accepted"><day>21</day><month>12</month><year>2018</year></date></history><permissions><copyright-statement>© The Author(s) 2019</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold> This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>.</license-p></license></permissions><abstract id="Abs1"><p id="Par1">Inactivated influenza vaccines (IIVs) lack broad efficacy. Cellular immunity to a conserved internal antigen, the nucleoprotein (NP), has been correlated to protection against pandemic and seasonal influenza and thus could have the potential to broaden vaccine efficacy. We developed OVX836, a recombinant protein vaccine based on an oligomerized NP, which shows increased uptake by dendritic cells and immunogenicity compared with NP. Intramuscular immunization in mice with OVX836 induced strong NP-specific CD4+ and CD8+ T-cell systemic responses and established CD8+ tissue memory T cells in the lung parenchyma. Strikingly, OVX836 protected mice against viral challenge with three different influenza A subtypes, isolated several decades apart and induced a reduction in viral load. When co-administered with IIV, OVX836 was even more effective in reducing lung viral load.</p></abstract><abstract id="Abs2" abstract-type="LongSummary"><title>Influenza vaccine: engineered nucleoprotein with improved protective efficacy against multiple strains</title><p id="Par2">Circulating influenza A virus (IAV) strains differ in their surface proteins each year, and vaccines eliciting an immune response to these proteins are often only partially protective. Internal viral proteins, such as the nucleoprotein (NP), are highly conserved, and cellular immunity to NP has been correlated with protection from diverse strains. However, current IAV vaccines induce a poor immune response to NP. In this study, led by Fergal Hill from Osivax, researchers develop an oligomeric version of NP with improved immunogenicity. Vaccination of mice with oligomeric NP results in an improved NP-specific T-cell response, including CD8<sup>+</sup> tissue memory T cells in the lung, and protects mice against three different IAV subtypes. Co-administration with the currently used inactivated influenza vaccine further improves protection against virus infection in mice. These results encourage further pre-clinical and clinical development for this vaccine candidate.</p></abstract><funding-group><award-group><funding-source><institution>ARN Funded Project "OPTIVAC" DS0404</institution></funding-source></award-group></funding-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2019</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc><affiliations><list><country><li>Canada</li><li>France</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Rhône-Alpes</li></region><settlement><li>Lyon</li></settlement></list><tree><noCountry><name sortKey="Pizzorno, Andres" sort="Pizzorno, Andres" uniqKey="Pizzorno A" first="Andres" last="Pizzorno">Andres Pizzorno</name><name sortKey="Rosa Calatrava, Manuel" sort="Rosa Calatrava, Manuel" uniqKey="Rosa Calatrava M" first="Manuel" last="Rosa-Calatrava">Manuel Rosa-Calatrava</name></noCountry><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Del Campo, Judith" sort="Del Campo, Judith" uniqKey="Del Campo J" first="Judith" last="Del Campo">Judith Del Campo</name></region><name sortKey="Bouley, Julien" sort="Bouley, Julien" uniqKey="Bouley J" first="Julien" last="Bouley">Julien Bouley</name><name sortKey="Djebali, Sophia" sort="Djebali, Sophia" uniqKey="Djebali S" first="Sophia" last="Djebali">Sophia Djebali</name><name sortKey="Haller, Marjorie" sort="Haller, Marjorie" uniqKey="Haller M" first="Marjorie" last="Haller">Marjorie Haller</name><name sortKey="Hill, Fergal" sort="Hill, Fergal" uniqKey="Hill F" first="Fergal" last="Hill">Fergal Hill</name><name sortKey="Le Vert, Alexandre" sort="Le Vert, Alexandre" uniqKey="Le Vert A" first="Alexandre" last="Le Vert">Alexandre Le Vert</name><name sortKey="Leverrier, Yann" sort="Leverrier, Yann" uniqKey="Leverrier Y" first="Yann" last="Leverrier">Yann Leverrier</name><name sortKey="Lina, Bruno" sort="Lina, Bruno" uniqKey="Lina B" first="Bruno" last="Lina">Bruno Lina</name><name sortKey="Marvel, Jacqueline" sort="Marvel, Jacqueline" uniqKey="Marvel J" first="Jacqueline" last="Marvel">Jacqueline Marvel</name><name sortKey="Nicolas, Florence" sort="Nicolas, Florence" uniqKey="Nicolas F" first="Florence" last="Nicolas">Florence Nicolas</name><name sortKey="Perez Vargas, Jimena" sort="Perez Vargas, Jimena" uniqKey="Perez Vargas J" first="Jimena" last="Pérez-Vargas">Jimena Pérez-Vargas</name><name sortKey="Perez Vargas, Jimena" sort="Perez Vargas, Jimena" uniqKey="Perez Vargas J" first="Jimena" last="Pérez-Vargas">Jimena Pérez-Vargas</name></country><country name="Canada"><noRegion><name sortKey="Boivin, Guy" sort="Boivin, Guy" uniqKey="Boivin G" first="Guy" last="Boivin">Guy Boivin</name></noRegion><name sortKey="Hamelin, Marie Eve" sort="Hamelin, Marie Eve" uniqKey="Hamelin M" first="Marie-Eve" last="Hamelin">Marie-Eve Hamelin</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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