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Article: The development and characterization of H5 influenza virus vaccines derived from a 2003 human isolate

TitleThe development and characterization of H5 influenza virus vaccines derived from a 2003 human isolate
Authors
Issue Date2006
PublisherElsevier Ltd. The Journal's web site is located at http://www.elsevier.com/locate/vaccine
Citation
Vaccine, 2006, v. 24 n. 17, p. 3669-3676 How to Cite?
AbstractThe pandemic threat posed by highly pathogenic H5N1 influenza A viruses has created an urgent need for vaccines to protect against H5 virus infection. Because pathogenic viruses grow poorly in chicken eggs and their virulence poses a biohazard to vaccine producers, avirulent viruses produced by reverse genetics have become the preferred basis for vaccine production. Here, we investigated two key characteristics of potential H5 vaccine candidates: the hemaggutinin (HA) cleavage site sequence and its modification to attenuate virulence and the choice of background virus to provide a high-growth rate. We produced recombinant (6:2 reassortant) viruses that possessed a series of modified avirulent-type HA and neuraminidase genes, both of which were derived from an H5N1 human isolate. The other genes of these recombinant viruses were derived from donor virus strains known to grow well in eggs: the human strain A/Puerto Rico/8/34 (PR8) or an avian strain. All of the recombinant viruses grew well in eggs, were avirulent in chicks, and protected animals against infection with a wild-type virus. However, one of the recombinant viruses with an avian virus background acquired a mutation in the HA cleavage site sequence that conferred virulence potential to this virus. Moreover, vaccine candidates with the avian virus background were more virulent than those with the human virus background. We conclude that 6:2 recombinant viruses with a PR8 background are more suitable than those with an avian virus background for vaccine development and that the HA cleavage site sequence must be modified to minimize the potential for a vaccine virus to convert to a virulent form. © 2006 Elsevier Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/179789
ISSN
2015 Impact Factor: 3.413
2015 SCImago Journal Rankings: 2.044
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorHorimoto, Ten_US
dc.contributor.authorTakada, Aen_US
dc.contributor.authorFujii, Ken_US
dc.contributor.authorGoto, Hen_US
dc.contributor.authorHatta, Men_US
dc.contributor.authorWatanabe, Sen_US
dc.contributor.authorIwatsuki-Horimoto, Ken_US
dc.contributor.authorIto, Men_US
dc.contributor.authorTagawa-Sakai, Yen_US
dc.contributor.authorYamada, Sen_US
dc.contributor.authorIto, Ten_US
dc.contributor.authorImai, Men_US
dc.contributor.authorItamura, Sen_US
dc.contributor.authorOdagiri, Ten_US
dc.contributor.authorTashiro, Men_US
dc.contributor.authorLim, WWLen_US
dc.contributor.authorGuan, Yen_US
dc.contributor.authorPeiris, JSMen_US
dc.contributor.authorKawaoka, Yen_US
dc.date.accessioned2012-12-19T10:04:44Z-
dc.date.available2012-12-19T10:04:44Z-
dc.date.issued2006en_US
dc.identifier.citationVaccine, 2006, v. 24 n. 17, p. 3669-3676en_US
dc.identifier.issn0264-410Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/179789-
dc.description.abstractThe pandemic threat posed by highly pathogenic H5N1 influenza A viruses has created an urgent need for vaccines to protect against H5 virus infection. Because pathogenic viruses grow poorly in chicken eggs and their virulence poses a biohazard to vaccine producers, avirulent viruses produced by reverse genetics have become the preferred basis for vaccine production. Here, we investigated two key characteristics of potential H5 vaccine candidates: the hemaggutinin (HA) cleavage site sequence and its modification to attenuate virulence and the choice of background virus to provide a high-growth rate. We produced recombinant (6:2 reassortant) viruses that possessed a series of modified avirulent-type HA and neuraminidase genes, both of which were derived from an H5N1 human isolate. The other genes of these recombinant viruses were derived from donor virus strains known to grow well in eggs: the human strain A/Puerto Rico/8/34 (PR8) or an avian strain. All of the recombinant viruses grew well in eggs, were avirulent in chicks, and protected animals against infection with a wild-type virus. However, one of the recombinant viruses with an avian virus background acquired a mutation in the HA cleavage site sequence that conferred virulence potential to this virus. Moreover, vaccine candidates with the avian virus background were more virulent than those with the human virus background. We conclude that 6:2 recombinant viruses with a PR8 background are more suitable than those with an avian virus background for vaccine development and that the HA cleavage site sequence must be modified to minimize the potential for a vaccine virus to convert to a virulent form. © 2006 Elsevier Ltd. All rights reserved.en_US
dc.languageengen_US
dc.publisherElsevier Ltd. The Journal's web site is located at http://www.elsevier.com/locate/vaccineen_US
dc.relation.ispartofVaccineen_US
dc.rightsVaccine. Copyright © Elsevier Ltd.-
dc.subject.meshAnimalsen_US
dc.subject.meshCell Lineen_US
dc.subject.meshChick Embryoen_US
dc.subject.meshFemaleen_US
dc.subject.meshHemagglutinin Glycoproteins, Influenza Virus - Genetics - Immunologyen_US
dc.subject.meshHumansen_US
dc.subject.meshInfluenza A Virus, H5n1 Subtype - Growth & Development - Immunology - Pathogenicityen_US
dc.subject.meshInfluenza Vaccines - Immunologyen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred Balb Cen_US
dc.subject.meshNeuraminidase - Genetics - Immunologyen_US
dc.subject.meshReassortant Viruses - Immunologyen_US
dc.subject.meshVaccines, Synthetic - Immunologyen_US
dc.subject.meshVirulenceen_US
dc.titleThe development and characterization of H5 influenza virus vaccines derived from a 2003 human isolateen_US
dc.typeArticleen_US
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hken_US
dc.identifier.emailPeiris, M: malik@hkucc.hku.hken_US
dc.identifier.authorityGuan, Y=rp00397en_US
dc.identifier.authorityPeiris, M=rp00410en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.vaccine.2005.07.005en_US
dc.identifier.pmid16378663-
dc.identifier.scopuseid_2-s2.0-33645210445en_US
dc.identifier.hkuros116509-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33645210445&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume24en_US
dc.identifier.issue17en_US
dc.identifier.spage3669en_US
dc.identifier.epage3676en_US
dc.identifier.isiWOS:000237005400034-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridHorimoto, T=7004547083en_US
dc.identifier.scopusauthoridTakada, A=7202962935en_US
dc.identifier.scopusauthoridFujii, K=35352613700en_US
dc.identifier.scopusauthoridGoto, H=7401676007en_US
dc.identifier.scopusauthoridHatta, M=7004521317en_US
dc.identifier.scopusauthoridWatanabe, S=35371645500en_US
dc.identifier.scopusauthoridIwatsukiHorimoto, K=6603276128en_US
dc.identifier.scopusauthoridIto, M=12791429700en_US
dc.identifier.scopusauthoridTagawaSakai, Y=12792889700en_US
dc.identifier.scopusauthoridYamada, S=35418940500en_US
dc.identifier.scopusauthoridIto, H=7407940875en_US
dc.identifier.scopusauthoridIto, T=7410326060en_US
dc.identifier.scopusauthoridImai, M=35426243300en_US
dc.identifier.scopusauthoridItamura, S=6603845258en_US
dc.identifier.scopusauthoridOdagiri, T=7005759915en_US
dc.identifier.scopusauthoridTashiro, M=7201482415en_US
dc.identifier.scopusauthoridLim, W=7202378277en_US
dc.identifier.scopusauthoridGuan, Y=7202924055en_US
dc.identifier.scopusauthoridPeiris, M=7005486823en_US
dc.identifier.scopusauthoridKawaoka, Y=26643027000en_US

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