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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Immunogenicity of modified vaccinia virus Ankara expressing the hemagglutinin stalk domain of pandemic (H1N1) 2009 influenza virus</title><author><name sortKey="Di Mario, Giuseppina" sort="Di Mario, Giuseppina" uniqKey="Di Mario G" first="Giuseppina" last="Di Mario">Giuseppina Di Mario</name><affiliation><nlm:aff id="af1">Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Soprana, Elisa" sort="Soprana, Elisa" uniqKey="Soprana E" first="Elisa" last="Soprana">Elisa Soprana</name><affiliation><nlm:aff id="af2">Molecular Immunology Unit, San Raffaele Research Institute, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Gubinelli, Francesco" sort="Gubinelli, Francesco" uniqKey="Gubinelli F" first="Francesco" last="Gubinelli">Francesco Gubinelli</name><affiliation><nlm:aff id="af2">Molecular Immunology Unit, San Raffaele Research Institute, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Panigada, Maddalena" sort="Panigada, Maddalena" uniqKey="Panigada M" first="Maddalena" last="Panigada">Maddalena Panigada</name><affiliation><nlm:aff id="af2">Molecular Immunology Unit, San Raffaele Research Institute, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Facchini, Marzia" sort="Facchini, Marzia" uniqKey="Facchini M" first="Marzia" last="Facchini">Marzia Facchini</name><affiliation><nlm:aff id="af1">Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Fabiani, Concetta" sort="Fabiani, Concetta" uniqKey="Fabiani C" first="Concetta" last="Fabiani">Concetta Fabiani</name><affiliation><nlm:aff id="af1">Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Garulli, Bruno" sort="Garulli, Bruno" uniqKey="Garulli B" first="Bruno" last="Garulli">Bruno Garulli</name><affiliation><nlm:aff id="af3">Department of Biology and Biotechnology “Charles Darwin”, Sapienza University of Rome, Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Basileo, Michela" sort="Basileo, Michela" uniqKey="Basileo M" first="Michela" last="Basileo">Michela Basileo</name><affiliation><nlm:aff id="af4">Polo d’Innovazione della Genomica, Genetica e Biologia, University of Perugia, Perugia, Italy</nlm:aff></affiliation></author><author><name sortKey="Cassone, Antonio" sort="Cassone, Antonio" uniqKey="Cassone A" first="Antonio" last="Cassone">Antonio Cassone</name><affiliation><nlm:aff id="af4">Polo d’Innovazione della Genomica, Genetica e Biologia, University of Perugia, Perugia, Italy</nlm:aff></affiliation></author><author><name sortKey="Siccardi, Antonio" sort="Siccardi, Antonio" uniqKey="Siccardi A" first="Antonio" last="Siccardi">Antonio Siccardi</name><affiliation><nlm:aff id="af2">Molecular Immunology Unit, San Raffaele Research Institute, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Donatelli, Isabella" sort="Donatelli, Isabella" uniqKey="Donatelli I" first="Isabella" last="Donatelli">Isabella Donatelli</name><affiliation><nlm:aff id="af1">Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Castrucci, Maria R" sort="Castrucci, Maria R" uniqKey="Castrucci M" first="Maria R." last="Castrucci">Maria R. Castrucci</name><affiliation><nlm:aff id="af1">Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">28081672</idno><idno type="pmc">5375617</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5375617</idno><idno type="RBID">PMC:5375617</idno><idno type="doi">10.1080/20477724.2016.1275464</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">000739</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000739</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Immunogenicity of modified vaccinia virus Ankara expressing the hemagglutinin stalk domain of pandemic (H1N1) 2009 influenza virus</title><author><name sortKey="Di Mario, Giuseppina" sort="Di Mario, Giuseppina" uniqKey="Di Mario G" first="Giuseppina" last="Di Mario">Giuseppina Di Mario</name><affiliation><nlm:aff id="af1">Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Soprana, Elisa" sort="Soprana, Elisa" uniqKey="Soprana E" first="Elisa" last="Soprana">Elisa Soprana</name><affiliation><nlm:aff id="af2">Molecular Immunology Unit, San Raffaele Research Institute, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Gubinelli, Francesco" sort="Gubinelli, Francesco" uniqKey="Gubinelli F" first="Francesco" last="Gubinelli">Francesco Gubinelli</name><affiliation><nlm:aff id="af2">Molecular Immunology Unit, San Raffaele Research Institute, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Panigada, Maddalena" sort="Panigada, Maddalena" uniqKey="Panigada M" first="Maddalena" last="Panigada">Maddalena Panigada</name><affiliation><nlm:aff id="af2">Molecular Immunology Unit, San Raffaele Research Institute, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Facchini, Marzia" sort="Facchini, Marzia" uniqKey="Facchini M" first="Marzia" last="Facchini">Marzia Facchini</name><affiliation><nlm:aff id="af1">Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Fabiani, Concetta" sort="Fabiani, Concetta" uniqKey="Fabiani C" first="Concetta" last="Fabiani">Concetta Fabiani</name><affiliation><nlm:aff id="af1">Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Garulli, Bruno" sort="Garulli, Bruno" uniqKey="Garulli B" first="Bruno" last="Garulli">Bruno Garulli</name><affiliation><nlm:aff id="af3">Department of Biology and Biotechnology “Charles Darwin”, Sapienza University of Rome, Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Basileo, Michela" sort="Basileo, Michela" uniqKey="Basileo M" first="Michela" last="Basileo">Michela Basileo</name><affiliation><nlm:aff id="af4">Polo d’Innovazione della Genomica, Genetica e Biologia, University of Perugia, Perugia, Italy</nlm:aff></affiliation></author><author><name sortKey="Cassone, Antonio" sort="Cassone, Antonio" uniqKey="Cassone A" first="Antonio" last="Cassone">Antonio Cassone</name><affiliation><nlm:aff id="af4">Polo d’Innovazione della Genomica, Genetica e Biologia, University of Perugia, Perugia, Italy</nlm:aff></affiliation></author><author><name sortKey="Siccardi, Antonio" sort="Siccardi, Antonio" uniqKey="Siccardi A" first="Antonio" last="Siccardi">Antonio Siccardi</name><affiliation><nlm:aff id="af2">Molecular Immunology Unit, San Raffaele Research Institute, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Donatelli, Isabella" sort="Donatelli, Isabella" uniqKey="Donatelli I" first="Isabella" last="Donatelli">Isabella Donatelli</name><affiliation><nlm:aff id="af1">Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy</nlm:aff></affiliation></author><author><name sortKey="Castrucci, Maria R" sort="Castrucci, Maria R" uniqKey="Castrucci M" first="Maria R." last="Castrucci">Maria R. Castrucci</name><affiliation><nlm:aff id="af1">Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy</nlm:aff></affiliation></author></analytic><series><title level="j">Pathogens and Global Health</title><idno type="ISSN">2047-7724</idno><idno type="eISSN">2047-7732</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background:</bold> Vaccination offers protection against influenza, although current vaccines need to be reformulated each year. The development of a broadly protective influenza vaccine would guarantee the induction of heterosubtypic immunity also against emerging influenza viruses of a novel subtype. Vaccine candidates based on the stalk region of the hemagglutinin (HA) have the potential to induce broad and persistent protection against diverse influenza A viruses.</p><p><bold>Methods:</bold> Modified vaccinia virus Ankara (MVA) expressing a headless HA (hlHA) of A/California/4/09 (CA/09) virus was used as a vaccine to immunize C57BL/6 mice. Specific antibody and cell-mediated immune responses were determined, and challenge experiments were performed by infecting vaccinated mice with CA/09 virus.</p><p><bold>Results</bold>: Immunization of mice with CA/09-derived hlHA, vectored by MVA, was able to elicit influenza-specific broad cross-reactive antibodies and cell-mediated immune responses, but failed to induce neutralizing antibodies and did not protect mice against virus challenge.</p><p><bold>Conclusion</bold>: Although highly immunogenic, our vaccine was unable to induce a protective immunity against influenza. A misfolded and unstable conformation of the hlHA molecule may have affected its capacity of inducing neutralizing antiviral, conformational antibodies. Design of stable hlHA-based immunogens and their delivery by recombinant MVA-based vectors has the potential of improving this promising approach for a universal influenza vaccine.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Pathog Glob Health</journal-id><journal-id journal-id-type="iso-abbrev">Pathog Glob Health</journal-id><journal-id journal-id-type="publisher-id">YPGH</journal-id><journal-title-group><journal-title>Pathogens and Global Health</journal-title></journal-title-group><issn pub-type="ppub">2047-7724</issn><issn pub-type="epub">2047-7732</issn><publisher><publisher-name>Taylor & Francis</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28081672</article-id><article-id pub-id-type="pmc">5375617</article-id><article-id pub-id-type="publisher-id">ypgh-111-69</article-id><article-id pub-id-type="doi">10.1080/20477724.2016.1275464</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Articles</subject></subj-group></article-categories><title-group><article-title>Immunogenicity of modified vaccinia virus Ankara expressing the hemagglutinin stalk domain of pandemic (H1N1) 2009 influenza virus</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Di Mario</surname><given-names>Giuseppina</given-names></name><xref ref-type="aff" rid="af1">a</xref></contrib><contrib contrib-type="author"><name><surname>Soprana</surname><given-names>Elisa</given-names></name><xref ref-type="aff" rid="af2">b</xref></contrib><contrib contrib-type="author"><name><surname>Gubinelli</surname><given-names>Francesco</given-names></name><xref ref-type="aff" rid="af2">b</xref></contrib><contrib contrib-type="author"><name><surname>Panigada</surname><given-names>Maddalena</given-names></name><xref ref-type="aff" rid="af2">b</xref></contrib><contrib contrib-type="author"><name><surname>Facchini</surname><given-names>Marzia</given-names></name><xref ref-type="aff" rid="af1">a</xref></contrib><contrib contrib-type="author"><name><surname>Fabiani</surname><given-names>Concetta</given-names></name><xref ref-type="aff" rid="af1">a</xref></contrib><contrib contrib-type="author"><name><surname>Garulli</surname><given-names>Bruno</given-names></name><xref ref-type="aff" rid="af3">c</xref></contrib><contrib contrib-type="author"><name><surname>Basileo</surname><given-names>Michela</given-names></name><xref ref-type="aff" rid="af4">d</xref></contrib><contrib contrib-type="author"><name><surname>Cassone</surname><given-names>Antonio</given-names></name><xref ref-type="aff" rid="af4">d</xref></contrib><contrib contrib-type="author"><name><surname>Siccardi</surname><given-names>Antonio</given-names></name><xref ref-type="aff" rid="af2">b</xref></contrib><contrib contrib-type="author"><name><surname>Donatelli</surname><given-names>Isabella</given-names></name><xref ref-type="aff" rid="af1">a</xref></contrib><contrib contrib-type="author"><name><surname>Castrucci</surname><given-names>Maria R.</given-names></name><xref ref-type="aff" rid="af1">a</xref><xref ref-type="corresp" rid="COR0001"></xref></contrib></contrib-group><aff id="af1"><label>a</label>Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy</aff><aff id="af2"><label>b</label>Molecular Immunology Unit, San Raffaele Research Institute, Milan, Italy</aff><aff id="af3"><label>c</label>Department of Biology and Biotechnology “Charles Darwin”, Sapienza University of Rome, Rome, Italy</aff><aff id="af4"><label>d</label>Polo d’Innovazione della Genomica, Genetica e Biologia, University of Perugia, Perugia, Italy</aff><author-notes><corresp id="COR0001">Corresponding author. Email: <email>mariarita.castrucci@iss.it</email></corresp></author-notes><pub-date pub-type="ppub"><month>3</month><year>2017</year></pub-date><pub-date pub-type="epub"><day>12</day><month>1</month><year>2017</year></pub-date><volume>111</volume><issue>2</issue><fpage seq="3">69</fpage><lpage>75</lpage><permissions><copyright-statement>© 2017 Informa UK Limited, trading as Taylor & Francis Group</copyright-statement><copyright-year>2017</copyright-year></permissions><self-uri content-type="pdf" xlink:href="ypgh-111-69.pdf"></self-uri><abstract><p><bold>Background:</bold> Vaccination offers protection against influenza, although current vaccines need to be reformulated each year. The development of a broadly protective influenza vaccine would guarantee the induction of heterosubtypic immunity also against emerging influenza viruses of a novel subtype. Vaccine candidates based on the stalk region of the hemagglutinin (HA) have the potential to induce broad and persistent protection against diverse influenza A viruses.</p><p><bold>Methods:</bold> Modified vaccinia virus Ankara (MVA) expressing a headless HA (hlHA) of A/California/4/09 (CA/09) virus was used as a vaccine to immunize C57BL/6 mice. Specific antibody and cell-mediated immune responses were determined, and challenge experiments were performed by infecting vaccinated mice with CA/09 virus.</p><p><bold>Results</bold>: Immunization of mice with CA/09-derived hlHA, vectored by MVA, was able to elicit influenza-specific broad cross-reactive antibodies and cell-mediated immune responses, but failed to induce neutralizing antibodies and did not protect mice against virus challenge.</p><p><bold>Conclusion</bold>: Although highly immunogenic, our vaccine was unable to induce a protective immunity against influenza. A misfolded and unstable conformation of the hlHA molecule may have affected its capacity of inducing neutralizing antiviral, conformational antibodies. Design of stable hlHA-based immunogens and their delivery by recombinant MVA-based vectors has the potential of improving this promising approach for a universal influenza vaccine.</p></abstract><kwd-group kwd-group-type="author"><kwd>Influenza virus</kwd><kwd>vaccine</kwd><kwd>antibodies</kwd><kwd>MVA vector</kwd></kwd-group><funding-group><award-group><funding-source><named-content content-type="funder-name">Fondazione Cariplo</named-content><named-content content-type="funder-identifier">10.13039/501100002803</named-content></funding-source><award-id>2009-3594</award-id></award-group><award-group><funding-source><named-content content-type="funder-name">Ministero della Salute</named-content><named-content content-type="funder-identifier">10.13039/501100003196</named-content></funding-source><award-id>UNIFLUVAC</award-id></award-group></funding-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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