Characterization of Reverse Genetics-Derived Cold-Adapted Master Donor Virus A/Leningrad/134/17/57 (H2N2) and Reassortants with H5N1 Surface Genes in a Mouse Model
Identifieur interne : 000615 ( Pmc/Corpus ); précédent : 000614; suivant : 000616Characterization of Reverse Genetics-Derived Cold-Adapted Master Donor Virus A/Leningrad/134/17/57 (H2N2) and Reassortants with H5N1 Surface Genes in a Mouse Model
Auteurs : Irina Isakova-Sivak ; Li-Mei Chen ; Melissa Bourgeois ; Yumiko Matsuoka ; J. Theo M. Voeten ; Jacco G. M. Heldens ; Han Van Den Bosch ; Alexander Klimov ; Larisa Rudenko ; Nancy J. Cox ; Ruben O. DonisSource :
- Clinical and Vaccine Immunology : CVI [ 1556-6811 ] ; 2014.
Abstract
Live attenuated influenza vaccines (LAIV) offer significant advantages over subunit or split inactivated vaccines to mitigate an eventual influenza pandemic, including simpler manufacturing processes and more cross-protective immune responses. Using an established reverse genetics (rg) system for wild-type (
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DOI: 10.1128/CVI.00819-13
PubMed: 24648485
PubMed Central: 4018889
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Characterization of Reverse Genetics-Derived Cold-Adapted Master Donor Virus A/Leningrad/134/17/57 (H2N2) and Reassortants with H5N1 Surface Genes in a Mouse Model</title>
<author><name sortKey="Isakova Sivak, Irina" sort="Isakova Sivak, Irina" uniqKey="Isakova Sivak I" first="Irina" last="Isakova-Sivak">Irina Isakova-Sivak</name>
<affiliation><nlm:aff id="aff1">Influenza Division, Centers for Disease Control and Prevention, Department of Health and Human Services, Atlanta, Georgia, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Institute of Experimental Medicine, Russian Academy of Medical Sciences, St. Petersburg, Russia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chen, Li Mei" sort="Chen, Li Mei" uniqKey="Chen L" first="Li-Mei" last="Chen">Li-Mei Chen</name>
<affiliation><nlm:aff id="aff1">Influenza Division, Centers for Disease Control and Prevention, Department of Health and Human Services, Atlanta, Georgia, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bourgeois, Melissa" sort="Bourgeois, Melissa" uniqKey="Bourgeois M" first="Melissa" last="Bourgeois">Melissa Bourgeois</name>
<affiliation><nlm:aff id="aff1">Influenza Division, Centers for Disease Control and Prevention, Department of Health and Human Services, Atlanta, Georgia, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Matsuoka, Yumiko" sort="Matsuoka, Yumiko" uniqKey="Matsuoka Y" first="Yumiko" last="Matsuoka">Yumiko Matsuoka</name>
<affiliation><nlm:aff id="aff1">Influenza Division, Centers for Disease Control and Prevention, Department of Health and Human Services, Atlanta, Georgia, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Voeten, J Theo M" sort="Voeten, J Theo M" uniqKey="Voeten J" first="J. Theo M." last="Voeten">J. Theo M. Voeten</name>
<affiliation><nlm:aff id="aff3">Nobilon International BV, Boxmeer, The Netherlands</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Heldens, Jacco G M" sort="Heldens, Jacco G M" uniqKey="Heldens J" first="Jacco G. M." last="Heldens">Jacco G. M. Heldens</name>
<affiliation><nlm:aff id="aff3">Nobilon International BV, Boxmeer, The Netherlands</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Van Den Bosch, Han" sort="Van Den Bosch, Han" uniqKey="Van Den Bosch H" first="Han" last="Van Den Bosch">Han Van Den Bosch</name>
<affiliation><nlm:aff id="aff3">Nobilon International BV, Boxmeer, The Netherlands</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Klimov, Alexander" sort="Klimov, Alexander" uniqKey="Klimov A" first="Alexander" last="Klimov">Alexander Klimov</name>
<affiliation><nlm:aff id="aff1">Influenza Division, Centers for Disease Control and Prevention, Department of Health and Human Services, Atlanta, Georgia, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rudenko, Larisa" sort="Rudenko, Larisa" uniqKey="Rudenko L" first="Larisa" last="Rudenko">Larisa Rudenko</name>
<affiliation><nlm:aff id="aff2">Institute of Experimental Medicine, Russian Academy of Medical Sciences, St. Petersburg, Russia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cox, Nancy J" sort="Cox, Nancy J" uniqKey="Cox N" first="Nancy J." last="Cox">Nancy J. Cox</name>
<affiliation><nlm:aff id="aff1">Influenza Division, Centers for Disease Control and Prevention, Department of Health and Human Services, Atlanta, Georgia, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Donis, Ruben O" sort="Donis, Ruben O" uniqKey="Donis R" first="Ruben O." last="Donis">Ruben O. Donis</name>
<affiliation><nlm:aff id="aff1">Influenza Division, Centers for Disease Control and Prevention, Department of Health and Human Services, Atlanta, Georgia, USA</nlm:aff>
</affiliation>
</author>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Characterization of Reverse Genetics-Derived Cold-Adapted Master Donor Virus A/Leningrad/134/17/57 (H2N2) and Reassortants with H5N1 Surface Genes in a Mouse Model</title>
<author><name sortKey="Isakova Sivak, Irina" sort="Isakova Sivak, Irina" uniqKey="Isakova Sivak I" first="Irina" last="Isakova-Sivak">Irina Isakova-Sivak</name>
<affiliation><nlm:aff id="aff1">Influenza Division, Centers for Disease Control and Prevention, Department of Health and Human Services, Atlanta, Georgia, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Institute of Experimental Medicine, Russian Academy of Medical Sciences, St. Petersburg, Russia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chen, Li Mei" sort="Chen, Li Mei" uniqKey="Chen L" first="Li-Mei" last="Chen">Li-Mei Chen</name>
<affiliation><nlm:aff id="aff1">Influenza Division, Centers for Disease Control and Prevention, Department of Health and Human Services, Atlanta, Georgia, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bourgeois, Melissa" sort="Bourgeois, Melissa" uniqKey="Bourgeois M" first="Melissa" last="Bourgeois">Melissa Bourgeois</name>
<affiliation><nlm:aff id="aff1">Influenza Division, Centers for Disease Control and Prevention, Department of Health and Human Services, Atlanta, Georgia, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Matsuoka, Yumiko" sort="Matsuoka, Yumiko" uniqKey="Matsuoka Y" first="Yumiko" last="Matsuoka">Yumiko Matsuoka</name>
<affiliation><nlm:aff id="aff1">Influenza Division, Centers for Disease Control and Prevention, Department of Health and Human Services, Atlanta, Georgia, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Voeten, J Theo M" sort="Voeten, J Theo M" uniqKey="Voeten J" first="J. Theo M." last="Voeten">J. Theo M. Voeten</name>
<affiliation><nlm:aff id="aff3">Nobilon International BV, Boxmeer, The Netherlands</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Heldens, Jacco G M" sort="Heldens, Jacco G M" uniqKey="Heldens J" first="Jacco G. M." last="Heldens">Jacco G. M. Heldens</name>
<affiliation><nlm:aff id="aff3">Nobilon International BV, Boxmeer, The Netherlands</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Van Den Bosch, Han" sort="Van Den Bosch, Han" uniqKey="Van Den Bosch H" first="Han" last="Van Den Bosch">Han Van Den Bosch</name>
<affiliation><nlm:aff id="aff3">Nobilon International BV, Boxmeer, The Netherlands</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Klimov, Alexander" sort="Klimov, Alexander" uniqKey="Klimov A" first="Alexander" last="Klimov">Alexander Klimov</name>
<affiliation><nlm:aff id="aff1">Influenza Division, Centers for Disease Control and Prevention, Department of Health and Human Services, Atlanta, Georgia, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rudenko, Larisa" sort="Rudenko, Larisa" uniqKey="Rudenko L" first="Larisa" last="Rudenko">Larisa Rudenko</name>
<affiliation><nlm:aff id="aff2">Institute of Experimental Medicine, Russian Academy of Medical Sciences, St. Petersburg, Russia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cox, Nancy J" sort="Cox, Nancy J" uniqKey="Cox N" first="Nancy J." last="Cox">Nancy J. Cox</name>
<affiliation><nlm:aff id="aff1">Influenza Division, Centers for Disease Control and Prevention, Department of Health and Human Services, Atlanta, Georgia, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Donis, Ruben O" sort="Donis, Ruben O" uniqKey="Donis R" first="Ruben O." last="Donis">Ruben O. Donis</name>
<affiliation><nlm:aff id="aff1">Influenza Division, Centers for Disease Control and Prevention, Department of Health and Human Services, Atlanta, Georgia, USA</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Clinical and Vaccine Immunology : CVI</title>
<idno type="ISSN">1556-6811</idno>
<idno type="eISSN">1556-679X</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
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<front><div type="abstract" xml:lang="en"><p>Live attenuated influenza vaccines (LAIV) offer significant advantages over subunit or split inactivated vaccines to mitigate an eventual influenza pandemic, including simpler manufacturing processes and more cross-protective immune responses. Using an established reverse genetics (rg) system for wild-type (<italic>wt</italic>
) A/Leningrad/134/1957 and cold-adapted (<italic>ca</italic>
) A/Leningrad/134/17/1957 (Len17) master donor virus (MDV), we produced and characterized three rg H5N1 reassortant viruses carrying modified HA and intact NA genes from either A/Vietnam/1203/2004 (H5N1, VN1203, clade 1) or A/Egypt/321/2007 (H5N1, EG321, clade 2) virus. A mouse model of infection was used to determine the infectivity and tissue tropism of the parental <italic>wt</italic>
viruses compared to the <italic>ca</italic>
master donor viruses as well as the H5N1 reassortants. All <italic>ca</italic>
viruses showed reduced replication in lungs and enhanced replication in nasal epithelium. In addition, the H5N1 HA and NA enhanced replication in lungs unless it was restricted by the internal genes of the <italic>ca</italic>
MDV. Mice inoculated twice 4 weeks apart with the H5N1 reassortant LAIV candidate viruses developed serum hemagglutination inhibition HI and IgA antibody titers to the homologous and heterologous viruses consistent with protective immunity. These animals remained healthy after challenge inoculation with a lethal dose with homologous or heterologous <italic>wt</italic>
H5N1 highly pathogenic avian influenza (HPAI) viruses. The profiles of viral replication in respiratory tissues and the immunogenicity and protective efficacy characteristics of the two <italic>ca</italic>
H5N1 candidate LAIV viruses warrant further development into a vaccine for human use.</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">Clin Vaccine Immunol</journal-id>
<journal-id journal-id-type="iso-abbrev">Clin. Vaccine Immunol</journal-id>
<journal-id journal-id-type="hwp">cdli</journal-id>
<journal-id journal-id-type="pmc">cvi</journal-id>
<journal-id journal-id-type="publisher-id">CVI</journal-id>
<journal-title-group><journal-title>Clinical and Vaccine Immunology : CVI</journal-title>
</journal-title-group>
<issn pub-type="ppub">1556-6811</issn>
<issn pub-type="epub">1556-679X</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">24648485</article-id>
<article-id pub-id-type="pmc">4018889</article-id>
<article-id pub-id-type="publisher-id">00819-13</article-id>
<article-id pub-id-type="doi">10.1128/CVI.00819-13</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Vaccines</subject>
</subj-group>
</article-categories>
<title-group><article-title>Characterization of Reverse Genetics-Derived Cold-Adapted Master Donor Virus A/Leningrad/134/17/57 (H2N2) and Reassortants with H5N1 Surface Genes in a Mouse Model</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Isakova-Sivak</surname>
<given-names>Irina</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chen</surname>
<given-names>Li-Mei</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bourgeois</surname>
<given-names>Melissa</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="author-notes" rid="fn1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Matsuoka</surname>
<given-names>Yumiko</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="author-notes" rid="fn1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Voeten</surname>
<given-names>J. Theo M.</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>c</sup>
</xref>
<xref ref-type="author-notes" rid="fn1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Heldens</surname>
<given-names>Jacco G. M.</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>c</sup>
</xref>
<xref ref-type="author-notes" rid="fn1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>van den Bosch</surname>
<given-names>Han</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>c</sup>
</xref>
<xref ref-type="author-notes" rid="fn1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Klimov</surname>
<given-names>Alexander</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="author-notes" rid="fn2">†</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rudenko</surname>
<given-names>Larisa</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cox</surname>
<given-names>Nancy J.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Donis</surname>
<given-names>Ruben O.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<aff id="aff1"><label>a</label>
Influenza Division, Centers for Disease Control and Prevention, Department of Health and Human Services, Atlanta, Georgia, USA</aff>
<aff id="aff2"><label>b</label>
Institute of Experimental Medicine, Russian Academy of Medical Sciences, St. Petersburg, Russia</aff>
<aff id="aff3"><label>c</label>
Nobilon International BV, Boxmeer, The Netherlands</aff>
</contrib-group>
<contrib-group><contrib contrib-type="editor"><name><surname>Plotkin</surname>
<given-names>S. A.</given-names>
</name>
<role>Editor</role>
</contrib>
</contrib-group>
<author-notes><corresp id="cor1">Address correspondence to Ruben O. Donis, <email>rvd6@cdc.gov</email>
.</corresp>
<fn id="fn1" fn-type="present-address"><label>*</label>
<p>Present address: Melissa Bourgeois, Merck Animal Health, Summit, New Jersey, USA; Yumiko Matsuoka, Laboratory of Infectious Diseases, NIAID, National Institutes of Health, Bethesda, Maryland, USA; J. Theo M. Voeten, Merck Animal Health, Summit, New Jersey, USA; Jacco G. M. Heldens, Merck Animal Health, Summit, New Jersey, USA; Han van den Bosch, Athena Institute, Free University, Amsterdam, The Netherlands.</p>
</fn>
<fn id="fn2" fn-type="deceased"><label>†</label>
<p>Deceased.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><month>5</month>
<year>2014</year>
</pub-date>
<volume>21</volume>
<issue>5</issue>
<fpage>722</fpage>
<lpage>731</lpage>
<history><date date-type="received"><day>26</day>
<month>12</month>
<year>2013</year>
</date>
<date date-type="rev-request"><day>21</day>
<month>1</month>
<year>2014</year>
</date>
<date date-type="accepted"><day>11</day>
<month>3</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="zcd00514000722.pdf"></self-uri>
<abstract><p>Live attenuated influenza vaccines (LAIV) offer significant advantages over subunit or split inactivated vaccines to mitigate an eventual influenza pandemic, including simpler manufacturing processes and more cross-protective immune responses. Using an established reverse genetics (rg) system for wild-type (<italic>wt</italic>
) A/Leningrad/134/1957 and cold-adapted (<italic>ca</italic>
) A/Leningrad/134/17/1957 (Len17) master donor virus (MDV), we produced and characterized three rg H5N1 reassortant viruses carrying modified HA and intact NA genes from either A/Vietnam/1203/2004 (H5N1, VN1203, clade 1) or A/Egypt/321/2007 (H5N1, EG321, clade 2) virus. A mouse model of infection was used to determine the infectivity and tissue tropism of the parental <italic>wt</italic>
viruses compared to the <italic>ca</italic>
master donor viruses as well as the H5N1 reassortants. All <italic>ca</italic>
viruses showed reduced replication in lungs and enhanced replication in nasal epithelium. In addition, the H5N1 HA and NA enhanced replication in lungs unless it was restricted by the internal genes of the <italic>ca</italic>
MDV. Mice inoculated twice 4 weeks apart with the H5N1 reassortant LAIV candidate viruses developed serum hemagglutination inhibition HI and IgA antibody titers to the homologous and heterologous viruses consistent with protective immunity. These animals remained healthy after challenge inoculation with a lethal dose with homologous or heterologous <italic>wt</italic>
H5N1 highly pathogenic avian influenza (HPAI) viruses. The profiles of viral replication in respiratory tissues and the immunogenicity and protective efficacy characteristics of the two <italic>ca</italic>
H5N1 candidate LAIV viruses warrant further development into a vaccine for human use.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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