Comparative Study of the Temperature Sensitive, Cold Adapted and Attenuated Mutations Present in the Master Donor Viruses of the Two Commercial Human Live Attenuated Influenza Vaccines
Identifieur interne : 001019 ( Ncbi/Merge ); précédent : 001018; suivant : 001020Comparative Study of the Temperature Sensitive, Cold Adapted and Attenuated Mutations Present in the Master Donor Viruses of the Two Commercial Human Live Attenuated Influenza Vaccines
Auteurs : Laura Rodriguez ; Pilar Blanco-Lobo ; Emma C. Reilly [États-Unis] ; Tatsuya Maehigashi ; Aitor Nogales ; Andrew Smith [États-Unis] ; David J. Topham [États-Unis] ; Stephen Dewhurst ; Baek Kim [Corée du Sud] ; Luis Martínez-SobridoSource :
- Viruses [ 1999-4915 ] ; 2019.
Abstract
Influenza viruses cause annual, seasonal infection across the globe. Vaccination represents the most effective strategy to prevent such infections and/or to reduce viral disease. Two major types of influenza vaccines are approved for human use: inactivated influenza vaccines (IIVs) and live attenuated influenza vaccines (LAIVs). Two Master Donor Virus (MDV) backbones have been used to create LAIVs against influenza A virus (IAV): the United States (US) A/Ann Arbor/6/60 (AA) and the Russian A/Leningrad/134/17/57 (Len) H2N2 viruses. The mutations responsible for the temperature sensitive (
Url:
DOI: 10.3390/v11100928
PubMed: 31658679
PubMed Central: 6832241
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PMC:6832241Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Comparative Study of the Temperature Sensitive, Cold Adapted and Attenuated Mutations Present in the Master Donor Viruses of the Two Commercial Human Live Attenuated Influenza Vaccines</title>
<author><name sortKey="Rodriguez, Laura" sort="Rodriguez, Laura" uniqKey="Rodriguez L" first="Laura" last="Rodriguez">Laura Rodriguez</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Blanco Lobo, Pilar" sort="Blanco Lobo, Pilar" uniqKey="Blanco Lobo P" first="Pilar" last="Blanco-Lobo">Pilar Blanco-Lobo</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Reilly, Emma C" sort="Reilly, Emma C" uniqKey="Reilly E" first="Emma C." last="Reilly">Emma C. Reilly</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="af2-viruses-11-00928">David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Maehigashi, Tatsuya" sort="Maehigashi, Tatsuya" uniqKey="Maehigashi T" first="Tatsuya" last="Maehigashi">Tatsuya Maehigashi</name>
<affiliation><nlm:aff id="af3-viruses-11-00928">Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, GA 30322, USA;<email>t.maehigashi@emory.edu</email>
(T.M.);<email>baek.kim@emory.edu</email>
(B.K.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nogales, Aitor" sort="Nogales, Aitor" uniqKey="Nogales A" first="Aitor" last="Nogales">Aitor Nogales</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Smith, Andrew" sort="Smith, Andrew" uniqKey="Smith A" first="Andrew" last="Smith">Andrew Smith</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="af4-viruses-11-00928">Medical Scientist Training Program (MSTP), University of Rochester, Rochester, New York, NY 14642, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Medical Scientist Training Program (MSTP), University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Topham, David J" sort="Topham, David J" uniqKey="Topham D" first="David J." last="Topham">David J. Topham</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="af2-viruses-11-00928">David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dewhurst, Stephen" sort="Dewhurst, Stephen" uniqKey="Dewhurst S" first="Stephen" last="Dewhurst">Stephen Dewhurst</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kim, Baek" sort="Kim, Baek" uniqKey="Kim B" first="Baek" last="Kim">Baek Kim</name>
<affiliation><nlm:aff id="af3-viruses-11-00928">Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, GA 30322, USA;<email>t.maehigashi@emory.edu</email>
(T.M.);<email>baek.kim@emory.edu</email>
(B.K.)</nlm:aff>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af5-viruses-11-00928">College of Pharmacy, Kyung-Hee University, Seoul 02447, Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>College of Pharmacy, Kyung-Hee University, Seoul 02447</wicri:regionArea>
<placeName><settlement type="city">Séoul</settlement>
<region type="capital">Région capitale de Séoul</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Martinez Sobrido, Luis" sort="Martinez Sobrido, Luis" uniqKey="Martinez Sobrido L" first="Luis" last="Martínez-Sobrido">Luis Martínez-Sobrido</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
</author>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Comparative Study of the Temperature Sensitive, Cold Adapted and Attenuated Mutations Present in the Master Donor Viruses of the Two Commercial Human Live Attenuated Influenza Vaccines</title>
<author><name sortKey="Rodriguez, Laura" sort="Rodriguez, Laura" uniqKey="Rodriguez L" first="Laura" last="Rodriguez">Laura Rodriguez</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Blanco Lobo, Pilar" sort="Blanco Lobo, Pilar" uniqKey="Blanco Lobo P" first="Pilar" last="Blanco-Lobo">Pilar Blanco-Lobo</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Reilly, Emma C" sort="Reilly, Emma C" uniqKey="Reilly E" first="Emma C." last="Reilly">Emma C. Reilly</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="af2-viruses-11-00928">David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Maehigashi, Tatsuya" sort="Maehigashi, Tatsuya" uniqKey="Maehigashi T" first="Tatsuya" last="Maehigashi">Tatsuya Maehigashi</name>
<affiliation><nlm:aff id="af3-viruses-11-00928">Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, GA 30322, USA;<email>t.maehigashi@emory.edu</email>
(T.M.);<email>baek.kim@emory.edu</email>
(B.K.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nogales, Aitor" sort="Nogales, Aitor" uniqKey="Nogales A" first="Aitor" last="Nogales">Aitor Nogales</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Smith, Andrew" sort="Smith, Andrew" uniqKey="Smith A" first="Andrew" last="Smith">Andrew Smith</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="af4-viruses-11-00928">Medical Scientist Training Program (MSTP), University of Rochester, Rochester, New York, NY 14642, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Medical Scientist Training Program (MSTP), University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Topham, David J" sort="Topham, David J" uniqKey="Topham D" first="David J." last="Topham">David J. Topham</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="af2-viruses-11-00928">David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dewhurst, Stephen" sort="Dewhurst, Stephen" uniqKey="Dewhurst S" first="Stephen" last="Dewhurst">Stephen Dewhurst</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kim, Baek" sort="Kim, Baek" uniqKey="Kim B" first="Baek" last="Kim">Baek Kim</name>
<affiliation><nlm:aff id="af3-viruses-11-00928">Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, GA 30322, USA;<email>t.maehigashi@emory.edu</email>
(T.M.);<email>baek.kim@emory.edu</email>
(B.K.)</nlm:aff>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af5-viruses-11-00928">College of Pharmacy, Kyung-Hee University, Seoul 02447, Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>College of Pharmacy, Kyung-Hee University, Seoul 02447</wicri:regionArea>
<placeName><settlement type="city">Séoul</settlement>
<region type="capital">Région capitale de Séoul</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Martinez Sobrido, Luis" sort="Martinez Sobrido, Luis" uniqKey="Martinez Sobrido L" first="Luis" last="Martínez-Sobrido">Luis Martínez-Sobrido</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Viruses</title>
<idno type="eISSN">1999-4915</idno>
<imprint><date when="2019">2019</date>
</imprint>
</series>
</biblStruct>
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<profileDesc><textClass></textClass>
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<front><div type="abstract" xml:lang="en"><p>Influenza viruses cause annual, seasonal infection across the globe. Vaccination represents the most effective strategy to prevent such infections and/or to reduce viral disease. Two major types of influenza vaccines are approved for human use: inactivated influenza vaccines (IIVs) and live attenuated influenza vaccines (LAIVs). Two Master Donor Virus (MDV) backbones have been used to create LAIVs against influenza A virus (IAV): the United States (US) A/Ann Arbor/6/60 (AA) and the Russian A/Leningrad/134/17/57 (Len) H2N2 viruses. The mutations responsible for the temperature sensitive (<italic>ts</italic>
), cold-adapted (<italic>ca</italic>
) and attenuated (<italic>att</italic>
) phenotypes of the two MDVs have been previously identified and genetically mapped. However, a direct comparison of the contribution of these residues to viral attenuation, immunogenicity and protection efficacy has not been conducted. Here, we compared the In vitro and in vivo phenotype of recombinant influenza A/Puerto Rico/8/34 H1N1 (PR8) viruses containing the <italic>ts, ca</italic>
and <italic>att</italic>
mutations of the US (PR8/AA) and the Russian (PR8/Len) MDVs. Our results show that PR8/Len is more attenuated in vivo than PR8/AA, although both viruses induced similar levels of humoral and cellular responses, and protection against homologous and heterologous viral challenges. Our findings support the feasibility of using a different virus backbone as MDV for the development of improved LAIVs for the prevention of IAV infections.</p>
</div>
</front>
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</TEI>
<double pmid="31658679"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Comparative Study of the Temperature Sensitive, Cold Adapted and Attenuated Mutations Present in the Master Donor Viruses of the Two Commercial Human Live Attenuated Influenza Vaccines</title>
<author><name sortKey="Rodriguez, Laura" sort="Rodriguez, Laura" uniqKey="Rodriguez L" first="Laura" last="Rodriguez">Laura Rodriguez</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Blanco Lobo, Pilar" sort="Blanco Lobo, Pilar" uniqKey="Blanco Lobo P" first="Pilar" last="Blanco-Lobo">Pilar Blanco-Lobo</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Reilly, Emma C" sort="Reilly, Emma C" uniqKey="Reilly E" first="Emma C." last="Reilly">Emma C. Reilly</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="af2-viruses-11-00928">David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Maehigashi, Tatsuya" sort="Maehigashi, Tatsuya" uniqKey="Maehigashi T" first="Tatsuya" last="Maehigashi">Tatsuya Maehigashi</name>
<affiliation><nlm:aff id="af3-viruses-11-00928">Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, GA 30322, USA;<email>t.maehigashi@emory.edu</email>
(T.M.);<email>baek.kim@emory.edu</email>
(B.K.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nogales, Aitor" sort="Nogales, Aitor" uniqKey="Nogales A" first="Aitor" last="Nogales">Aitor Nogales</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Smith, Andrew" sort="Smith, Andrew" uniqKey="Smith A" first="Andrew" last="Smith">Andrew Smith</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="af4-viruses-11-00928">Medical Scientist Training Program (MSTP), University of Rochester, Rochester, New York, NY 14642, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Medical Scientist Training Program (MSTP), University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Topham, David J" sort="Topham, David J" uniqKey="Topham D" first="David J." last="Topham">David J. Topham</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="af2-viruses-11-00928">David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dewhurst, Stephen" sort="Dewhurst, Stephen" uniqKey="Dewhurst S" first="Stephen" last="Dewhurst">Stephen Dewhurst</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kim, Baek" sort="Kim, Baek" uniqKey="Kim B" first="Baek" last="Kim">Baek Kim</name>
<affiliation><nlm:aff id="af3-viruses-11-00928">Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, GA 30322, USA;<email>t.maehigashi@emory.edu</email>
(T.M.);<email>baek.kim@emory.edu</email>
(B.K.)</nlm:aff>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af5-viruses-11-00928">College of Pharmacy, Kyung-Hee University, Seoul 02447, Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>College of Pharmacy, Kyung-Hee University, Seoul 02447</wicri:regionArea>
<placeName><settlement type="city">Séoul</settlement>
<region type="capital">Région capitale de Séoul</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Martinez Sobrido, Luis" sort="Martinez Sobrido, Luis" uniqKey="Martinez Sobrido L" first="Luis" last="Martínez-Sobrido">Luis Martínez-Sobrido</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
</author>
</titleStmt>
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<idno type="pmid">31658679</idno>
<idno type="pmc">6832241</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832241</idno>
<idno type="RBID">PMC:6832241</idno>
<idno type="doi">10.3390/v11100928</idno>
<date when="2019">2019</date>
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<idno type="wicri:Area/Pmc/Curation">000C50</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000C50</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000080</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000080</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Comparative Study of the Temperature Sensitive, Cold Adapted and Attenuated Mutations Present in the Master Donor Viruses of the Two Commercial Human Live Attenuated Influenza Vaccines</title>
<author><name sortKey="Rodriguez, Laura" sort="Rodriguez, Laura" uniqKey="Rodriguez L" first="Laura" last="Rodriguez">Laura Rodriguez</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Blanco Lobo, Pilar" sort="Blanco Lobo, Pilar" uniqKey="Blanco Lobo P" first="Pilar" last="Blanco-Lobo">Pilar Blanco-Lobo</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Reilly, Emma C" sort="Reilly, Emma C" uniqKey="Reilly E" first="Emma C." last="Reilly">Emma C. Reilly</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="af2-viruses-11-00928">David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Maehigashi, Tatsuya" sort="Maehigashi, Tatsuya" uniqKey="Maehigashi T" first="Tatsuya" last="Maehigashi">Tatsuya Maehigashi</name>
<affiliation><nlm:aff id="af3-viruses-11-00928">Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, GA 30322, USA;<email>t.maehigashi@emory.edu</email>
(T.M.);<email>baek.kim@emory.edu</email>
(B.K.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nogales, Aitor" sort="Nogales, Aitor" uniqKey="Nogales A" first="Aitor" last="Nogales">Aitor Nogales</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Smith, Andrew" sort="Smith, Andrew" uniqKey="Smith A" first="Andrew" last="Smith">Andrew Smith</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="af4-viruses-11-00928">Medical Scientist Training Program (MSTP), University of Rochester, Rochester, New York, NY 14642, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Medical Scientist Training Program (MSTP), University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Topham, David J" sort="Topham, David J" uniqKey="Topham D" first="David J." last="Topham">David J. Topham</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="af2-viruses-11-00928">David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dewhurst, Stephen" sort="Dewhurst, Stephen" uniqKey="Dewhurst S" first="Stephen" last="Dewhurst">Stephen Dewhurst</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kim, Baek" sort="Kim, Baek" uniqKey="Kim B" first="Baek" last="Kim">Baek Kim</name>
<affiliation><nlm:aff id="af3-viruses-11-00928">Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, GA 30322, USA;<email>t.maehigashi@emory.edu</email>
(T.M.);<email>baek.kim@emory.edu</email>
(B.K.)</nlm:aff>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="af5-viruses-11-00928">College of Pharmacy, Kyung-Hee University, Seoul 02447, Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>College of Pharmacy, Kyung-Hee University, Seoul 02447</wicri:regionArea>
<placeName><settlement type="city">Séoul</settlement>
<region type="capital">Région capitale de Séoul</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Martinez Sobrido, Luis" sort="Martinez Sobrido, Luis" uniqKey="Martinez Sobrido L" first="Luis" last="Martínez-Sobrido">Luis Martínez-Sobrido</name>
<affiliation><nlm:aff id="af1-viruses-11-00928">Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA;<email>laurita85oviedo@hotmail.com</email>
(L.R.);<email>piblanlo@gmail.com</email>
(P.B.-L.);<email>emma_reilly@urmc.rochester.edu</email>
(E.C.R.);<email>nogales.aitor@inia.es</email>
(A.N.);<email>Andrew_Smith72@URMC.Rochester.edu</email>
(A.S.);<email>David_topham@urmc.rochester.edu</email>
(D.J.T.);<email>stephen_dewhurst@me.com</email>
(S.D.)</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Viruses</title>
<idno type="eISSN">1999-4915</idno>
<imprint><date when="2019">2019</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Influenza viruses cause annual, seasonal infection across the globe. Vaccination represents the most effective strategy to prevent such infections and/or to reduce viral disease. Two major types of influenza vaccines are approved for human use: inactivated influenza vaccines (IIVs) and live attenuated influenza vaccines (LAIVs). Two Master Donor Virus (MDV) backbones have been used to create LAIVs against influenza A virus (IAV): the United States (US) A/Ann Arbor/6/60 (AA) and the Russian A/Leningrad/134/17/57 (Len) H2N2 viruses. The mutations responsible for the temperature sensitive (<italic>ts</italic>
), cold-adapted (<italic>ca</italic>
) and attenuated (<italic>att</italic>
) phenotypes of the two MDVs have been previously identified and genetically mapped. However, a direct comparison of the contribution of these residues to viral attenuation, immunogenicity and protection efficacy has not been conducted. Here, we compared the In vitro and in vivo phenotype of recombinant influenza A/Puerto Rico/8/34 H1N1 (PR8) viruses containing the <italic>ts, ca</italic>
and <italic>att</italic>
mutations of the US (PR8/AA) and the Russian (PR8/Len) MDVs. Our results show that PR8/Len is more attenuated in vivo than PR8/AA, although both viruses induced similar levels of humoral and cellular responses, and protection against homologous and heterologous viral challenges. Our findings support the feasibility of using a different virus backbone as MDV for the development of improved LAIVs for the prevention of IAV infections.</p>
</div>
</front>
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<author><name sortKey="Reich, S" uniqKey="Reich S">S. Reich</name>
</author>
<author><name sortKey="Naffakh, N" uniqKey="Naffakh N">N. Naffakh</name>
</author>
<author><name sortKey="Cusack, S" uniqKey="Cusack S">S. Cusack</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Delano, W L" uniqKey="Delano W">W.L. DeLano</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
</pmc>
<pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Comparative Study of the Temperature Sensitive, Cold Adapted and Attenuated Mutations Present in the Master Donor Viruses of the Two Commercial Human Live Attenuated Influenza Vaccines.</title>
<author><name sortKey="Rodriguez, Laura" sort="Rodriguez, Laura" uniqKey="Rodriguez L" first="Laura" last="Rodriguez">Laura Rodriguez</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA. laurita85oviedo@hotmail.com.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<wicri:noRegion>NY 14642</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Blanco Lobo, Pilar" sort="Blanco Lobo, Pilar" uniqKey="Blanco Lobo P" first="Pilar" last="Blanco-Lobo">Pilar Blanco-Lobo</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA. piblanlo@gmail.com.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<wicri:noRegion>NY 14642</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Reilly, Emma C" sort="Reilly, Emma C" uniqKey="Reilly E" first="Emma C" last="Reilly">Emma C. Reilly</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA. emma_reilly@urmc.rochester.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<wicri:noRegion>NY 14642</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Maehigashi, Tatsuya" sort="Maehigashi, Tatsuya" uniqKey="Maehigashi T" first="Tatsuya" last="Maehigashi">Tatsuya Maehigashi</name>
<affiliation wicri:level="1"><nlm:affiliation>Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, GA 30322, USA. t.maehigashi@emory.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, GA 30322</wicri:regionArea>
<wicri:noRegion>GA 30322</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Nogales, Aitor" sort="Nogales, Aitor" uniqKey="Nogales A" first="Aitor" last="Nogales">Aitor Nogales</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA. nogales.aitor@inia.es.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<wicri:noRegion>NY 14642</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Smith, Andrew" sort="Smith, Andrew" uniqKey="Smith A" first="Andrew" last="Smith">Andrew Smith</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA. Andrew_Smith72@URMC.Rochester.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<wicri:noRegion>NY 14642</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Topham, David J" sort="Topham, David J" uniqKey="Topham D" first="David J" last="Topham">David J. Topham</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA. David_topham@urmc.rochester.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<wicri:noRegion>NY 14642</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Dewhurst, Stephen" sort="Dewhurst, Stephen" uniqKey="Dewhurst S" first="Stephen" last="Dewhurst">Stephen Dewhurst</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA. stephen_dewhurst@me.com.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<wicri:noRegion>NY 14642</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kim, Baek" sort="Kim, Baek" uniqKey="Kim B" first="Baek" last="Kim">Baek Kim</name>
<affiliation wicri:level="1"><nlm:affiliation>Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, GA 30322, USA. baek.kim@emory.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, GA 30322</wicri:regionArea>
<wicri:noRegion>GA 30322</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Martinez Sobrido, Luis" sort="Martinez Sobrido, Luis" uniqKey="Martinez Sobrido L" first="Luis" last="Martínez-Sobrido">Luis Martínez-Sobrido</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA. luis_martinez@urmc.rochester.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<wicri:noRegion>NY 14642</wicri:noRegion>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2019">2019</date>
<idno type="RBID">pubmed:31658679</idno>
<idno type="pmid">31658679</idno>
<idno type="doi">10.3390/v11100928</idno>
<idno type="wicri:Area/PubMed/Corpus">000005</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000005</idno>
<idno type="wicri:Area/PubMed/Curation">000005</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000005</idno>
<idno type="wicri:Area/PubMed/Checkpoint">000011</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000011</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Comparative Study of the Temperature Sensitive, Cold Adapted and Attenuated Mutations Present in the Master Donor Viruses of the Two Commercial Human Live Attenuated Influenza Vaccines.</title>
<author><name sortKey="Rodriguez, Laura" sort="Rodriguez, Laura" uniqKey="Rodriguez L" first="Laura" last="Rodriguez">Laura Rodriguez</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA. laurita85oviedo@hotmail.com.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<wicri:noRegion>NY 14642</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Blanco Lobo, Pilar" sort="Blanco Lobo, Pilar" uniqKey="Blanco Lobo P" first="Pilar" last="Blanco-Lobo">Pilar Blanco-Lobo</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA. piblanlo@gmail.com.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<wicri:noRegion>NY 14642</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Reilly, Emma C" sort="Reilly, Emma C" uniqKey="Reilly E" first="Emma C" last="Reilly">Emma C. Reilly</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA. emma_reilly@urmc.rochester.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<wicri:noRegion>NY 14642</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Maehigashi, Tatsuya" sort="Maehigashi, Tatsuya" uniqKey="Maehigashi T" first="Tatsuya" last="Maehigashi">Tatsuya Maehigashi</name>
<affiliation wicri:level="1"><nlm:affiliation>Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, GA 30322, USA. t.maehigashi@emory.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, GA 30322</wicri:regionArea>
<wicri:noRegion>GA 30322</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Nogales, Aitor" sort="Nogales, Aitor" uniqKey="Nogales A" first="Aitor" last="Nogales">Aitor Nogales</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA. nogales.aitor@inia.es.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<wicri:noRegion>NY 14642</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Smith, Andrew" sort="Smith, Andrew" uniqKey="Smith A" first="Andrew" last="Smith">Andrew Smith</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA. Andrew_Smith72@URMC.Rochester.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<wicri:noRegion>NY 14642</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Topham, David J" sort="Topham, David J" uniqKey="Topham D" first="David J" last="Topham">David J. Topham</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA. David_topham@urmc.rochester.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<wicri:noRegion>NY 14642</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Dewhurst, Stephen" sort="Dewhurst, Stephen" uniqKey="Dewhurst S" first="Stephen" last="Dewhurst">Stephen Dewhurst</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA. stephen_dewhurst@me.com.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<wicri:noRegion>NY 14642</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kim, Baek" sort="Kim, Baek" uniqKey="Kim B" first="Baek" last="Kim">Baek Kim</name>
<affiliation wicri:level="1"><nlm:affiliation>Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, GA 30322, USA. baek.kim@emory.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, GA 30322</wicri:regionArea>
<wicri:noRegion>GA 30322</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Martinez Sobrido, Luis" sort="Martinez Sobrido, Luis" uniqKey="Martinez Sobrido L" first="Luis" last="Martínez-Sobrido">Luis Martínez-Sobrido</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA. luis_martinez@urmc.rochester.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642</wicri:regionArea>
<wicri:noRegion>NY 14642</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Viruses</title>
<idno type="eISSN">1999-4915</idno>
<imprint><date when="2019" type="published">2019</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Influenza viruses cause annual, seasonal infection across the globe. Vaccination represents the most effective strategy to prevent such infections and/or to reduce viral disease. Two major types of influenza vaccines are approved for human use: inactivated influenza vaccines (IIVs) and live attenuated influenza vaccines (LAIVs). Two Master Donor Virus (MDV) backbones have been used to create LAIVs against influenza A virus (IAV): the United States (US) A/Ann Arbor/6/60 (AA) and the Russian A/Leningrad/134/17/57 (Len) H2N2 viruses. The mutations responsible for the temperature sensitive (<i>ts</i>
), cold-adapted (<i>ca</i>
) and attenuated (<i>att</i>
) phenotypes of the two MDVs have been previously identified and genetically mapped. However, a direct comparison of the contribution of these residues to viral attenuation, immunogenicity and protection efficacy has not been conducted. Here, we compared the In vitro and in vivo phenotype of recombinant influenza A/Puerto Rico/8/34 H1N1 (PR8) viruses containing the <i>ts, ca</i>
and <i>att</i>
mutations of the US (PR8/AA) and the Russian (PR8/Len) MDVs. Our results show that PR8/Len is more attenuated in vivo than PR8/AA, although both viruses induced similar levels of humoral and cellular responses, and protection against homologous and heterologous viral challenges. Our findings support the feasibility of using a different virus backbone as MDV for the development of improved LAIVs for the prevention of IAV infections.</div>
</front>
</TEI>
</pubmed>
</double>
</record>
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