Broad Protection against Avian Influenza Virus by Using a Modified Vaccinia Ankara Virus Expressing a Mosaic Hemagglutinin Gene
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Auteurs : Attapon Kamlangdee [États-Unis] ; Brock Kingstad-Bakke [États-Unis] ; Tavis K. Anderson [États-Unis] ; Tony L. Goldberg [États-Unis] ; Jorge E. Osorio [États-Unis]Source :
- Journal of Virology [ 0022-538X ] ; 2014.
Abstract
A critical failure in our preparedness for an influenza pandemic is the lack of a universal vaccine. Influenza virus strains diverge by 1 to 2% per year, and commercially available vaccines often do not elicit protection from one year to the next, necessitating frequent formulation changes. This represents a major challenge to the development of a cross-protective vaccine that can protect against circulating viral antigenic diversity. We have constructed a recombinant modified vaccinia virus Ankara (MVA) that expresses an H5N1 mosaic hemagglutinin (H5M) (MVA-H5M). This mosaic was generated
Url:
DOI: 10.1128/JVI.01532-14
PubMed: 25210173
PubMed Central: 4249068
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<series><title level="j">Journal of Virology</title>
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<front><div type="abstract" xml:lang="en"><title>ABSTRACT</title>
<p>A critical failure in our preparedness for an influenza pandemic is the lack of a universal vaccine. Influenza virus strains diverge by 1 to 2% per year, and commercially available vaccines often do not elicit protection from one year to the next, necessitating frequent formulation changes. This represents a major challenge to the development of a cross-protective vaccine that can protect against circulating viral antigenic diversity. We have constructed a recombinant modified vaccinia virus Ankara (MVA) that expresses an H5N1 mosaic hemagglutinin (H5M) (MVA-H5M). This mosaic was generated <italic>in silico</italic>
using 2,145 field-sourced H5N1 isolates. A single dose of MVA-H5M provided 100% protection in mice against clade 0, 1, and 2 avian influenza viruses and also protected against seasonal H1N1 virus (A/Puerto Rico/8/34). It also provided short-term (10 days) and long-term (6 months) protection postvaccination. Both neutralizing antibodies and antigen-specific CD4<sup>+</sup>
and CD8<sup>+</sup>
T cells were still detected at 5 months postvaccination, suggesting that MVA-H5M provides long-lasting immunity.</p>
<p><bold>IMPORTANCE</bold>
Influenza viruses infect a billion people and cause up to 500,000 deaths every year. A major problem in combating influenza is the lack of broadly effective vaccines. One solution from the field of human immunodeficiency virus vaccinology involves a novel <italic>in silico</italic>
mosaic approach that has been shown to provide broad and robust protection against highly variable viruses. Unlike a consensus algorithm which picks the most frequent residue at each position, the mosaic method chooses the most frequent T-cell epitopes and combines them to form a synthetic antigen. These studies demonstrated that a mosaic influenza virus H5 hemagglutinin expressed by a viral vector can elicit full protection against diverse H5N1 challenges as well as induce broader immunity than a wild-type hemagglutinin.</p>
</div>
</front>
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<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">J Virol</journal-id>
<journal-id journal-id-type="iso-abbrev">J. Virol</journal-id>
<journal-id journal-id-type="hwp">jvi</journal-id>
<journal-id journal-id-type="pmc">jvi</journal-id>
<journal-id journal-id-type="publisher-id">JVI</journal-id>
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<issn pub-type="ppub">0022-538X</issn>
<issn pub-type="epub">1098-5514</issn>
<publisher><publisher-name>American Society for Microbiology</publisher-name>
<publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc>
</publisher>
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<article-meta><article-id pub-id-type="pmid">25210173</article-id>
<article-id pub-id-type="pmc">4249068</article-id>
<article-id pub-id-type="publisher-id">01532-14</article-id>
<article-id pub-id-type="doi">10.1128/JVI.01532-14</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Vaccines and Antiviral Agents</subject>
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<title-group><article-title>Broad Protection against Avian Influenza Virus by Using a Modified Vaccinia Ankara Virus Expressing a Mosaic Hemagglutinin Gene</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Kamlangdee</surname>
<given-names>Attapon</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kingstad-Bakke</surname>
<given-names>Brock</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Anderson</surname>
<given-names>Tavis K.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Goldberg</surname>
<given-names>Tony L.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Osorio</surname>
<given-names>Jorge E.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<aff id="aff1"><label>a</label>
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin—Madison, Madison, Wisconsin, USA</aff>
<aff id="aff2"><label>b</label>
Department of Biology, Georgia Southern University, Statesboro, Georgia, USA</aff>
</contrib-group>
<contrib-group><contrib contrib-type="editor"><name><surname>Lyles</surname>
<given-names>D. S.</given-names>
</name>
<role>Editor</role>
</contrib>
</contrib-group>
<author-notes><corresp id="cor1">Address correspondence to Jorge E. Osorio, <email>osorio@svm.vetmed.wisc.edu</email>
.</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>11</month>
<year>2014</year>
</pub-date>
<volume>88</volume>
<issue>22</issue>
<fpage>13300</fpage>
<lpage>13309</lpage>
<history><date date-type="received"><day>29</day>
<month>5</month>
<year>2014</year>
</date>
<date date-type="accepted"><day>26</day>
<month>8</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2014, American Society for Microbiology. All Rights Reserved.</copyright-statement>
<copyright-year>2014</copyright-year>
<copyright-holder>American Society for Microbiology</copyright-holder>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zjv02214013300.pdf"></self-uri>
<abstract><title>ABSTRACT</title>
<p>A critical failure in our preparedness for an influenza pandemic is the lack of a universal vaccine. Influenza virus strains diverge by 1 to 2% per year, and commercially available vaccines often do not elicit protection from one year to the next, necessitating frequent formulation changes. This represents a major challenge to the development of a cross-protective vaccine that can protect against circulating viral antigenic diversity. We have constructed a recombinant modified vaccinia virus Ankara (MVA) that expresses an H5N1 mosaic hemagglutinin (H5M) (MVA-H5M). This mosaic was generated <italic>in silico</italic>
using 2,145 field-sourced H5N1 isolates. A single dose of MVA-H5M provided 100% protection in mice against clade 0, 1, and 2 avian influenza viruses and also protected against seasonal H1N1 virus (A/Puerto Rico/8/34). It also provided short-term (10 days) and long-term (6 months) protection postvaccination. Both neutralizing antibodies and antigen-specific CD4<sup>+</sup>
and CD8<sup>+</sup>
T cells were still detected at 5 months postvaccination, suggesting that MVA-H5M provides long-lasting immunity.</p>
<p><bold>IMPORTANCE</bold>
Influenza viruses infect a billion people and cause up to 500,000 deaths every year. A major problem in combating influenza is the lack of broadly effective vaccines. One solution from the field of human immunodeficiency virus vaccinology involves a novel <italic>in silico</italic>
mosaic approach that has been shown to provide broad and robust protection against highly variable viruses. Unlike a consensus algorithm which picks the most frequent residue at each position, the mosaic method chooses the most frequent T-cell epitopes and combines them to form a synthetic antigen. These studies demonstrated that a mosaic influenza virus H5 hemagglutinin expressed by a viral vector can elicit full protection against diverse H5N1 challenges as well as induce broader immunity than a wild-type hemagglutinin.</p>
</abstract>
</article-meta>
</front>
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