Efficacy of an Adenoviral Vectored Multivalent Centralized Influenza Vaccine
Identifieur interne : 000E28 ( Ncbi/Merge ); précédent : 000E27; suivant : 000E29Efficacy of an Adenoviral Vectored Multivalent Centralized Influenza Vaccine
Auteurs : Amy Lingel ; Brianna L. Bullard ; Eric A. WeaverSource :
- Scientific Reports [ 2045-2322 ] ; 2017.
Abstract
Mice were immunized with Adenovirus expressing the H1-con, H2-con, H3-con and H5-con HA consensus genes in combination (multivalent) and compared to mice immunized with the traditional 2010–2011 FluZone and FluMist seasonal vaccines. Immunized mice were challenged with 10–100 MLD50 of H1N1, H3N1, H3N2 and H5N1 influenza viruses. The traditional vaccines induced robust levels of HA inhibition (HI) titers, but failed to protect against five different heterologous lethal influenza challenges. Conversely, the multivalent consensus vaccine (1 × 1010 virus particles (vp)/mouse) induced protective HI titers of ≥40 against 8 of 10 influenza viruses that represent a wide degree of divergence within the HA subtypes and protected 100% of mice from 8 of 9 lethal heterologous influenza virus challenges. The vaccine protection was dose dependent, in general, and a dose as low as 5 × 107 vp/mouse still provided 100% survival against 7 of 9 lethal heterologous influenza challenges. These data indicate that very low doses of Adenovirus-vectored consensus vaccines induce superior levels of immunity against a wide divergence of influenza subtypes as compared to traditional vaccines. These doses are scalable and translatable to humans and may provide the foundation for complete and long-lasting anti-influenza immunity.
Url:
DOI: 10.1038/s41598-017-14891-y
PubMed: 29097763
PubMed Central: 5668234
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Weaver</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">29097763</idno><idno type="pmc">5668234</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668234</idno><idno type="RBID">PMC:5668234</idno><idno type="doi">10.1038/s41598-017-14891-y</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">000197</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000197</idno><idno type="wicri:Area/Pmc/Curation">000197</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000197</idno><idno type="wicri:Area/Pmc/Checkpoint">000244</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000244</idno><idno type="wicri:Area/Ncbi/Merge">000E28</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Efficacy of an Adenoviral Vectored Multivalent Centralized Influenza Vaccine</title><author><name sortKey="Lingel, Amy" sort="Lingel, Amy" uniqKey="Lingel A" first="Amy" last="Lingel">Amy Lingel</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Bullard, Brianna L" sort="Bullard, Brianna L" uniqKey="Bullard B" first="Brianna L." last="Bullard">Brianna L. Bullard</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Weaver, Eric A" sort="Weaver, Eric A" uniqKey="Weaver E" first="Eric A." last="Weaver">Eric A. Weaver</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</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 id="Par1">Mice were immunized with Adenovirus expressing the H1-con, H2-con, H3-con and H5-con HA consensus genes in combination (multivalent) and compared to mice immunized with the traditional 2010–2011 FluZone and FluMist seasonal vaccines. Immunized mice were challenged with 10–100 MLD<sub>50</sub> of H1N1, H3N1, H3N2 and H5N1 influenza viruses. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Sci Rep</journal-id><journal-id journal-id-type="iso-abbrev">Sci Rep</journal-id><journal-title-group><journal-title>Scientific Reports</journal-title></journal-title-group><issn pub-type="epub">2045-2322</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">29097763</article-id><article-id pub-id-type="pmc">5668234</article-id><article-id pub-id-type="publisher-id">14891</article-id><article-id pub-id-type="doi">10.1038/s41598-017-14891-y</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Efficacy of an Adenoviral Vectored Multivalent Centralized Influenza Vaccine</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Lingel</surname><given-names>Amy</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Bullard</surname><given-names>Brianna L.</given-names></name><xref ref-type="aff" rid="Aff1"></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Weaver</surname><given-names>Eric A.</given-names></name><address><email>eweaver2@unl.edu</email></address><xref ref-type="aff" rid="Aff1"></xref></contrib><aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1937 0060</institution-id><institution-id institution-id-type="GRID">grid.24434.35</institution-id><institution>School of Biological Sciences, Nebraska Center for Virology, University of Nebraska,</institution></institution-wrap>Lincoln, USA</aff></contrib-group><pub-date pub-type="epub"><day>2</day><month>11</month><year>2017</year></pub-date><pub-date pub-type="pmc-release"><day>2</day><month>11</month><year>2017</year></pub-date><pub-date pub-type="collection"><year>2017</year></pub-date><volume>7</volume><elocation-id>14912</elocation-id><history><date date-type="received"><day>2</day><month>2</month><year>2017</year></date><date date-type="accepted"><day>18</day><month>10</month><year>2017</year></date></history><permissions><copyright-statement>© The Author(s) 2017</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">Mice were immunized with Adenovirus expressing the H1-con, H2-con, H3-con and H5-con HA consensus genes in combination (multivalent) and compared to mice immunized with the traditional 2010–2011 FluZone and FluMist seasonal vaccines. Immunized mice were challenged with 10–100 MLD<sub>50</sub> of H1N1, H3N1, H3N2 and H5N1 influenza viruses. The traditional vaccines induced robust levels of HA inhibition (HI) titers, but failed to protect against five different heterologous lethal influenza challenges. Conversely, the multivalent consensus vaccine (1 × 10<sup>10</sup> virus particles (vp)/mouse) induced protective HI titers of ≥40 against 8 of 10 influenza viruses that represent a wide degree of divergence within the HA subtypes and protected 100% of mice from 8 of 9 lethal heterologous influenza virus challenges. The vaccine protection was dose dependent, in general, and a dose as low as 5 × 10<sup>7</sup> vp/mouse still provided 100% survival against 7 of 9 lethal heterologous influenza challenges. These data indicate that very low doses of Adenovirus-vectored consensus vaccines induce superior levels of immunity against a wide divergence of influenza subtypes as compared to traditional vaccines. These doses are scalable and translatable to humans and may provide the foundation for complete and long-lasting anti-influenza immunity.</p></abstract><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2017</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc><affiliations><list></list><tree><noCountry><name sortKey="Bullard, Brianna L" sort="Bullard, Brianna L" uniqKey="Bullard B" first="Brianna L." last="Bullard">Brianna L. Bullard</name><name sortKey="Lingel, Amy" sort="Lingel, Amy" uniqKey="Lingel A" first="Amy" last="Lingel">Amy Lingel</name><name sortKey="Weaver, Eric A" sort="Weaver, Eric A" uniqKey="Weaver E" first="Eric A." last="Weaver">Eric A. Weaver</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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