Alternative Live-Attenuated Influenza Vaccines Based on Modifications in the Polymerase Genes Protect against Epidemic and Pandemic Flu
Identifieur interne : 000F92 ( Main/Exploration ); précédent : 000F91; suivant : 000F93Alternative Live-Attenuated Influenza Vaccines Based on Modifications in the Polymerase Genes Protect against Epidemic and Pandemic Flu
Auteurs : Alicia Solorzano [États-Unis] ; JIANQIANG YE [États-Unis] ; Daniel R. Perez [États-Unis]Source :
- Journal of virology [ 0022-538X ] ; 2010.
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Abstract
Human influenza is a seasonal disease associated with significant morbidity and mortality. Influenza vaccination is the most effective means for disease prevention. We have previously shown that mutations in the PB1 and PB2 genes of the live-attenuated influenza vaccine (LAIV) from the cold-adapted (ca) influenza virus A/Ann Arbor/6/60 (H2N2) could be transferred to avian influenza viruses and produce partially attenuated viruses. We also demonstrated that avian influenza viruses carrying the PB1 and PB2 mutations could be further attenuated by stably introducing a hemagglutinin (HA) epitope tag in the PB1 gene. In this work, we wanted to determine whether these modifications would also result in attenuation of a so-called triple reassortant (TR) swine influenza virus (SIV). Thus, the TR influenza A/swine/Wisconsin/14094/99 (H3N2) virus was generated by reverse genetics and subsequently mutated in the PB1 and PB2 genes. Here we show that a combination of mutations in this TR backbone results in an attenuated virus in vitro and in vivo. Furthermore, we show the potential of our TR backbone as a vaccine that provides protection against the 2009 swine-origin pandemic influenza H1N1 virus (S-OIV) when carrying the surface of a classical swine strain. We propose that the availability of alternative backbones to the conventional ca A/Ann Arbor/6/60 LAIV strain could also be useful in epidemic and pandemic influenza and should be considered for influenza vaccine development. In addition, our data provide evidence that the use of these alternative backbones could potentially circumvent the effects of original antigenic sin (OAS) in certain circumstances.
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Perez</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Virginia-Maryland Regional College of Veterinary Medicine and Department of Veterinary Medicine, University of Maryland, 8075 Greenmead Drive</s1><s2>College Park, Maryland 20742</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>College Park, Maryland 20742</wicri:noRegion><orgName type="university">Université du Maryland</orgName><placeName><settlement type="city">College Park (Maryland)</settlement><region type="state">Maryland</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Attenuated strain</term><term>Epidemic</term><term>Gene</term><term>Influenza</term><term>Vaccine</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Souche atténuée</term><term>Vaccin</term><term>Gène</term><term>Epidémie</term><term>Grippe</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Vaccin</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Human influenza is a seasonal disease associated with significant morbidity and mortality. Influenza vaccination is the most effective means for disease prevention. We have previously shown that mutations in the PB1 and PB2 genes of the live-attenuated influenza vaccine (LAIV) from the cold-adapted (ca) influenza virus A/Ann Arbor/6/60 (H2N2) could be transferred to avian influenza viruses and produce partially attenuated viruses. We also demonstrated that avian influenza viruses carrying the PB1 and PB2 mutations could be further attenuated by stably introducing a hemagglutinin (HA) epitope tag in the PB1 gene. In this work, we wanted to determine whether these modifications would also result in attenuation of a so-called triple reassortant (TR) swine influenza virus (SIV). Thus, the TR influenza A/swine/Wisconsin/14094/99 (H3N2) virus was generated by reverse genetics and subsequently mutated in the PB1 and PB2 genes. Here we show that a combination of mutations in this TR backbone results in an attenuated virus in vitro and in vivo. Furthermore, we show the potential of our TR backbone as a vaccine that provides protection against the 2009 swine-origin pandemic influenza H1N1 virus (S-OIV) when carrying the surface of a classical swine strain. We propose that the availability of alternative backbones to the conventional ca A/Ann Arbor/6/60 LAIV strain could also be useful in epidemic and pandemic influenza and should be considered for influenza vaccine development. In addition, our data provide evidence that the use of these alternative backbones could potentially circumvent the effects of original antigenic sin (OAS) in certain circumstances.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li></region><settlement><li>College Park (Maryland)</li></settlement><orgName><li>Université du Maryland</li></orgName></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Solorzano, Alicia" sort="Solorzano, Alicia" uniqKey="Solorzano A" first="Alicia" last="Solorzano">Alicia Solorzano</name></region><name sortKey="Jianqiang Ye" sort="Jianqiang Ye" uniqKey="Jianqiang Ye" last="Jianqiang Ye">JIANQIANG YE</name><name sortKey="Perez, Daniel R" sort="Perez, Daniel R" uniqKey="Perez D" first="Daniel R." last="Perez">Daniel R. Perez</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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