A Reassortment-Incompetent Live Attenuated Influenza Virus Vaccine for Protection against Pandemic Virus Strains▿
Identifieur interne : 000646 ( Ncbi/Merge ); précédent : 000645; suivant : 000647A Reassortment-Incompetent Live Attenuated Influenza Virus Vaccine for Protection against Pandemic Virus Strains▿
Auteurs : Rong Hai ; Adolfo García-Sastre [États-Unis] ; David E. Swayne [États-Unis] ; Peter Palese [États-Unis]Source :
- Journal of Virology [ 0022-538X ] ; 2011.
Abstract
Although live-attenuated influenza vaccines (LAIV) are safe for use in protection against seasonal influenza strains, concerns regarding their potential to reassort with wild-type virus strains have been voiced. LAIVs have been demonstrated to induce enhanced mucosal and cell-mediated immunity better than inactivated vaccines while also requiring a smaller dose to achieve a protective immune response. To address the need for a reassortment-incompetent live influenza A virus vaccine, we have designed a chimeric virus that takes advantage of the fact that influenza A and B viruses do not reassort. Our novel vaccine prototype uses an attenuated influenza B virus that has been manipulated to express the ectodomain of the influenza A hemagglutinin protein, the major target for eliciting neutralizing antibodies. The hemagglutinin RNA segment is modified such that it contains influenza B packaging signals, and therefore it cannot be incorporated into a wild-type influenza A virus. We have applied our strategy to different influenza A virus subtypes and generated chimeric B/PR8 HA (H1), HK68 (H3), and VN (H5) viruses. All recombinant viruses were attenuated both
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DOI: 10.1128/JVI.00609-11
PubMed: 21543486
PubMed Central: 3126605
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<series><title level="j">Journal of Virology</title>
<idno type="ISSN">0022-538X</idno>
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<imprint><date when="2011">2011</date>
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<front><div type="abstract" xml:lang="en"><p>Although live-attenuated influenza vaccines (LAIV) are safe for use in protection against seasonal influenza strains, concerns regarding their potential to reassort with wild-type virus strains have been voiced. LAIVs have been demonstrated to induce enhanced mucosal and cell-mediated immunity better than inactivated vaccines while also requiring a smaller dose to achieve a protective immune response. To address the need for a reassortment-incompetent live influenza A virus vaccine, we have designed a chimeric virus that takes advantage of the fact that influenza A and B viruses do not reassort. Our novel vaccine prototype uses an attenuated influenza B virus that has been manipulated to express the ectodomain of the influenza A hemagglutinin protein, the major target for eliciting neutralizing antibodies. The hemagglutinin RNA segment is modified such that it contains influenza B packaging signals, and therefore it cannot be incorporated into a wild-type influenza A virus. We have applied our strategy to different influenza A virus subtypes and generated chimeric B/PR8 HA (H1), HK68 (H3), and VN (H5) viruses. All recombinant viruses were attenuated both <italic>in vitro</italic>
and <italic>in vivo</italic>
, and immunization with these recombinant viruses protected mice against lethal influenza A virus infection. Overall, our data indicate that the chimeric live-attenuated influenza B viruses expressing the modified influenza A hemagglutinin are effective LAIVs.</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">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>
<journal-title-group><journal-title>Journal of Virology</journal-title>
</journal-title-group>
<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>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">21543486</article-id>
<article-id pub-id-type="pmc">3126605</article-id>
<article-id pub-id-type="publisher-id">0609-11</article-id>
<article-id pub-id-type="doi">10.1128/JVI.00609-11</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Vaccines and Antiviral Agents</subject>
</subj-group>
</article-categories>
<title-group><article-title>A Reassortment-Incompetent Live Attenuated Influenza Virus Vaccine for Protection against Pandemic Virus Strains<xref ref-type="fn" rid="FN1">▿</xref>
</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Hai</surname>
<given-names>Rong</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>García-Sastre</surname>
<given-names>Adolfo</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Swayne</surname>
<given-names>David E.</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Palese</surname>
<given-names>Peter</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<aff id="aff1"><label>1</label>
Department of Microbiology</aff>
<aff id="aff2"><label>2</label>
Institute of Global Health and Emerging Pathogens</aff>
<aff id="aff3"><label>3</label>
Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, New York, New York</aff>
<aff id="aff4"><label>4</label>
USDA-ARS, Southeast Poultry Research Laboratory, Exotic and Emerging Avian Viral Diseases Research Unit, Athens, Georgia 30605-2195</aff>
</contrib-group>
<author-notes><corresp id="cor1"><label>*</label>
Corresponding author. Mailing address: <addr-line>Department of Microbiology, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029-6574</addr-line>
. Phone: <phone>(212) 241-7318</phone>
. Fax: <fax>(212) 722-3634</fax>
. E-mail: <email>peter.palese@mssm.edu</email>
.</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>7</month>
<year>2011</year>
</pub-date>
<volume>85</volume>
<issue>14</issue>
<fpage>6832</fpage>
<lpage>6843</lpage>
<history><date date-type="received"><day>27</day>
<month>3</month>
<year>2011</year>
</date>
<date date-type="accepted"><day>26</day>
<month>4</month>
<year>2011</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2011, American Society for Microbiology</copyright-statement>
<copyright-year>2011</copyright-year>
<copyright-holder>American Society for Microbiology</copyright-holder>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zjv01411006832.pdf"></self-uri>
<abstract><p>Although live-attenuated influenza vaccines (LAIV) are safe for use in protection against seasonal influenza strains, concerns regarding their potential to reassort with wild-type virus strains have been voiced. LAIVs have been demonstrated to induce enhanced mucosal and cell-mediated immunity better than inactivated vaccines while also requiring a smaller dose to achieve a protective immune response. To address the need for a reassortment-incompetent live influenza A virus vaccine, we have designed a chimeric virus that takes advantage of the fact that influenza A and B viruses do not reassort. Our novel vaccine prototype uses an attenuated influenza B virus that has been manipulated to express the ectodomain of the influenza A hemagglutinin protein, the major target for eliciting neutralizing antibodies. The hemagglutinin RNA segment is modified such that it contains influenza B packaging signals, and therefore it cannot be incorporated into a wild-type influenza A virus. We have applied our strategy to different influenza A virus subtypes and generated chimeric B/PR8 HA (H1), HK68 (H3), and VN (H5) viruses. All recombinant viruses were attenuated both <italic>in vitro</italic>
and <italic>in vivo</italic>
, and immunization with these recombinant viruses protected mice against lethal influenza A virus infection. Overall, our data indicate that the chimeric live-attenuated influenza B viruses expressing the modified influenza A hemagglutinin are effective LAIVs.</p>
</abstract>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>États-Unis</li>
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<li>État de New York</li>
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<tree><noCountry><name sortKey="Hai, Rong" sort="Hai, Rong" uniqKey="Hai R" first="Rong" last="Hai">Rong Hai</name>
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<country name="États-Unis"><region name="État de New York"><name sortKey="Garcia Sastre, Adolfo" sort="Garcia Sastre, Adolfo" uniqKey="Garcia Sastre A" first="Adolfo" last="García-Sastre">Adolfo García-Sastre</name>
</region>
<name sortKey="Palese, Peter" sort="Palese, Peter" uniqKey="Palese P" first="Peter" last="Palese">Peter Palese</name>
<name sortKey="Swayne, David E" sort="Swayne, David E" uniqKey="Swayne D" first="David E." last="Swayne">David E. Swayne</name>
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