OVX836 a recombinant nucleoprotein vaccine inducing cellular responses and protective efficacy against multiple influenza A subtypes
Identifieur interne : 000061 ( Main/Exploration ); précédent : 000060; suivant : 000062OVX836 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.
Url:
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="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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Townsend</name></author></analytic></biblStruct></listBibl></div1></back></TEI><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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