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Article: Responsiveness to a pandemic alert: Use of reverse genetics for rapid development of influenza vaccines

TitleResponsiveness to a pandemic alert: Use of reverse genetics for rapid development of influenza vaccines
Authors
Issue Date2004
PublisherThe Lancet Publishing Group. The Journal's web site is located at http://www.elsevier.com/locate/lancet
Citation
Lancet, 2004, v. 363 n. 9415, p. 1099-1103 How to Cite?
AbstractBackground In response to the emergence of severe infection capable of rapid global spread, WHO will issue a pandemic alert. Such alerts are rare; however, on Feb 19, 2003, a pandemic alert was issued in response to human infections caused by an avian H5N1 influenza virus, A/Hong Kong/213/03. H5N1 had been noted once before in human beings in 1997 and killed a third (6/18) of infected people.1,2 The 2003 variant seemed to have been transmitted directly from birds to human beings and caused fatal pneumonia in one of two infected individuals. Candidate vaccines were sought, but no avirulent viruses antigenically similar to the pathogen were available, and the isolate killed embryonated chicken eggs. Since traditional strategies of vaccine production were not viable, we sought to produce a candidate reference virus using reverse genetics. Methods We removed the polybasic aminoacids that are associated with high virulence from the haemagglutinin cleavage site of A/Hong Kong/213/03 using influenza reverse genetics techniques. A reference vaccine virus was then produced on an A/Puerto Rico/8/34 (PR8) backbone on WHO-approved Vero cells. We assessed this reference virus for pathogenicity in in-vivo and in-vitro assays. Findings A reference vaccine virus was produced in Good Manufacturing Practice (GMP)-grade facilities in less than 4 weeks from the time of virus isolation. This virus proved to be non-pathogenic in chickens and ferrets and was shown to be stable after multiple passages in embryonated chicken eggs. Interpretation The ability to produce a candidate reference virus in such a short period of time sets a new standard for rapid response to emerging infectious disease threats and clearly shows the usefulness of reverse genetics for influenza vaccine development. The same technologies and procedures are currently being used to create reference vaccine viruses against the 2004 H5N1 viruses circulating in Asia.
Persistent Identifierhttp://hdl.handle.net/10722/79296
ISSN
2015 Impact Factor: 44.002
2015 SCImago Journal Rankings: 14.638
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWebby, RJen_HK
dc.contributor.authorPerez, DRen_HK
dc.contributor.authorColeman, JSen_HK
dc.contributor.authorGuan, Yen_HK
dc.contributor.authorKnight, JHen_HK
dc.contributor.authorGovorkova, EAen_HK
dc.contributor.authorMcClainMoss, LRen_HK
dc.contributor.authorPeiris, JSen_HK
dc.contributor.authorRehg, JEen_HK
dc.contributor.authorTuomanen, EIen_HK
dc.contributor.authorWebster, RGen_HK
dc.date.accessioned2010-09-06T07:52:58Z-
dc.date.available2010-09-06T07:52:58Z-
dc.date.issued2004en_HK
dc.identifier.citationLancet, 2004, v. 363 n. 9415, p. 1099-1103en_HK
dc.identifier.issn0140-6736en_HK
dc.identifier.urihttp://hdl.handle.net/10722/79296-
dc.description.abstractBackground In response to the emergence of severe infection capable of rapid global spread, WHO will issue a pandemic alert. Such alerts are rare; however, on Feb 19, 2003, a pandemic alert was issued in response to human infections caused by an avian H5N1 influenza virus, A/Hong Kong/213/03. H5N1 had been noted once before in human beings in 1997 and killed a third (6/18) of infected people.1,2 The 2003 variant seemed to have been transmitted directly from birds to human beings and caused fatal pneumonia in one of two infected individuals. Candidate vaccines were sought, but no avirulent viruses antigenically similar to the pathogen were available, and the isolate killed embryonated chicken eggs. Since traditional strategies of vaccine production were not viable, we sought to produce a candidate reference virus using reverse genetics. Methods We removed the polybasic aminoacids that are associated with high virulence from the haemagglutinin cleavage site of A/Hong Kong/213/03 using influenza reverse genetics techniques. A reference vaccine virus was then produced on an A/Puerto Rico/8/34 (PR8) backbone on WHO-approved Vero cells. We assessed this reference virus for pathogenicity in in-vivo and in-vitro assays. Findings A reference vaccine virus was produced in Good Manufacturing Practice (GMP)-grade facilities in less than 4 weeks from the time of virus isolation. This virus proved to be non-pathogenic in chickens and ferrets and was shown to be stable after multiple passages in embryonated chicken eggs. Interpretation The ability to produce a candidate reference virus in such a short period of time sets a new standard for rapid response to emerging infectious disease threats and clearly shows the usefulness of reverse genetics for influenza vaccine development. The same technologies and procedures are currently being used to create reference vaccine viruses against the 2004 H5N1 viruses circulating in Asia.en_HK
dc.languageengen_HK
dc.publisherThe Lancet Publishing Group. The Journal's web site is located at http://www.elsevier.com/locate/lanceten_HK
dc.relation.ispartofLanceten_HK
dc.titleResponsiveness to a pandemic alert: Use of reverse genetics for rapid development of influenza vaccinesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0140-6736&volume=363&issue=9415&spage=1099&epage=103&date=2004&atitle=Responsiveness+to+a+pandemic+alert:+use+of+reverse+genetics+for+rapid+development+of+influenza+vaccines.en_HK
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hken_HK
dc.identifier.emailPeiris, JS: malik@hkucc.hku.hken_HK
dc.identifier.authorityGuan, Y=rp00397en_HK
dc.identifier.authorityPeiris, JS=rp00410en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/S0140-6736(04)15892-3en_HK
dc.identifier.pmid15064027-
dc.identifier.scopuseid_2-s2.0-11144356405en_HK
dc.identifier.hkuros87584en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-11144356405&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume363en_HK
dc.identifier.issue9415en_HK
dc.identifier.spage1099en_HK
dc.identifier.epage1103en_HK
dc.identifier.isiWOS:000220595500008-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridWebby, RJ=35448064800en_HK
dc.identifier.scopusauthoridPerez, DR=7101996480en_HK
dc.identifier.scopusauthoridColeman, JS=7402803788en_HK
dc.identifier.scopusauthoridGuan, Y=7202924055en_HK
dc.identifier.scopusauthoridKnight, JH=7401751807en_HK
dc.identifier.scopusauthoridGovorkova, EA=7003837718en_HK
dc.identifier.scopusauthoridMcClainMoss, LR=6504065126en_HK
dc.identifier.scopusauthoridPeiris, JS=7005486823en_HK
dc.identifier.scopusauthoridRehg, JE=7004835777en_HK
dc.identifier.scopusauthoridTuomanen, EI=35517655700en_HK
dc.identifier.scopusauthoridWebster, RG=36048363100en_HK

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