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Article: Broad cross-protection against H5N1 avian influenza virus infection by means of monoclonal antibodies that map to conserved viral epitopes

TitleBroad cross-protection against H5N1 avian influenza virus infection by means of monoclonal antibodies that map to conserved viral epitopes
Authors
Issue Date2009
PublisherOxford University Press. The Journal's web site is located at http://jid.oxfordjournals.org
Citation
Journal of Infectious Diseases, 2009, v. 199 n. 1, p. 49-58 How to Cite?
AbstractBackground. Passive immunization with human H5 antisera or H5-specific monoclonal antibodies (MAbs) has potential as an effective treatment for acute H5N1 influenza virus infection, but its efficacy against antigenically diverse H5N1 viruses is unconfirmed. Methods. Cross-protection against antigenically diverse H5N1 strains with H5-specific MAbs, generated by successive immunization of antigenically distinct strains, was evaluated in mice. Results. A panel of 52 broadly cross-reactive H5 specific MAbs were generated and characterized. One of these MAbs, 13D4, has been demonstrated to protect mice against lethal challenge by 4 H5N1 strains representing the current major genetic populations, clades 1, 2.1, 2.2, and 2.3, even at a stage of infection when H5N1 virus has disseminated beyond the pulmonary system. Complete neutralization of virus in lung tissue of infected animals was observed 24 h after treatment with 13D4. Mapping of this MAb with escape mutants showed it to bind to 2 conserved, possibly critical, sites of H5N1 hemagglutinin, 152 and 182. Conclusion. Generation of broadly cross-protective MAbs against H5N1 influenza virus may be optimized by selecting MAbs that target conserved sites in hemagglutinin. H5 MAbs such as 13D4 may prove to have therapeutic value in controlling infection due to current and future H5N1 variants. © 2008 by the Infectious Diseases Society of America. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/157539
ISSN
2014 Impact Factor: 5.997
2014 SCImago Journal Rankings: 3.190
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChen, Yen_HK
dc.contributor.authorQin, Ken_HK
dc.contributor.authorWu, WLen_HK
dc.contributor.authorLi, Gen_HK
dc.contributor.authorZhang, Jen_HK
dc.contributor.authorDu, Hen_HK
dc.contributor.authorNg, MHen_HK
dc.contributor.authorShih, JWKen_HK
dc.contributor.authorPeiris, JSMen_HK
dc.contributor.authorGuan, Yen_HK
dc.contributor.authorChen, Hen_HK
dc.contributor.authorXia, Nen_HK
dc.date.accessioned2012-08-08T08:51:04Z-
dc.date.available2012-08-08T08:51:04Z-
dc.date.issued2009en_HK
dc.identifier.citationJournal of Infectious Diseases, 2009, v. 199 n. 1, p. 49-58en_HK
dc.identifier.issn0022-1899en_HK
dc.identifier.urihttp://hdl.handle.net/10722/157539-
dc.description.abstractBackground. Passive immunization with human H5 antisera or H5-specific monoclonal antibodies (MAbs) has potential as an effective treatment for acute H5N1 influenza virus infection, but its efficacy against antigenically diverse H5N1 viruses is unconfirmed. Methods. Cross-protection against antigenically diverse H5N1 strains with H5-specific MAbs, generated by successive immunization of antigenically distinct strains, was evaluated in mice. Results. A panel of 52 broadly cross-reactive H5 specific MAbs were generated and characterized. One of these MAbs, 13D4, has been demonstrated to protect mice against lethal challenge by 4 H5N1 strains representing the current major genetic populations, clades 1, 2.1, 2.2, and 2.3, even at a stage of infection when H5N1 virus has disseminated beyond the pulmonary system. Complete neutralization of virus in lung tissue of infected animals was observed 24 h after treatment with 13D4. Mapping of this MAb with escape mutants showed it to bind to 2 conserved, possibly critical, sites of H5N1 hemagglutinin, 152 and 182. Conclusion. Generation of broadly cross-protective MAbs against H5N1 influenza virus may be optimized by selecting MAbs that target conserved sites in hemagglutinin. H5 MAbs such as 13D4 may prove to have therapeutic value in controlling infection due to current and future H5N1 variants. © 2008 by the Infectious Diseases Society of America. All rights reserved.en_HK
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://jid.oxfordjournals.orgen_HK
dc.relation.ispartofJournal of Infectious Diseasesen_HK
dc.subject.meshAnimalsen_US
dc.subject.meshAntibodies, Monoclonal - Immunologyen_US
dc.subject.meshBirds - Virologyen_US
dc.subject.meshBody Weighten_US
dc.subject.meshChick Embryo - Virologyen_US
dc.subject.meshConserved Sequenceen_US
dc.subject.meshCross Reactionsen_US
dc.subject.meshEpitopes - Immunologyen_US
dc.subject.meshHemagglutination Inhibition Testsen_US
dc.subject.meshHumansen_US
dc.subject.meshInfluenza A Virus, H5N1 Subtype - Classification - Genetics - Immunology - Isolation & Purificationen_US
dc.subject.meshInfluenza Vaccines - Therapeutic Useen_US
dc.subject.meshInfluenza In Birds - Immunologyen_US
dc.subject.meshInfluenza, Human - Immunology - Mortality - Pathologyen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred Balb Cen_US
dc.titleBroad cross-protection against H5N1 avian influenza virus infection by means of monoclonal antibodies that map to conserved viral epitopesen_HK
dc.typeArticleen_HK
dc.identifier.emailWu, WL: hazelwu@hkucc.hku.hken_HK
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hken_HK
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hken_HK
dc.identifier.emailChen, H: hlchen@hku.hk-
dc.identifier.authorityPeiris, JSM=rp00410en_HK
dc.identifier.authorityGuan, Y=rp00397en_HK
dc.identifier.authorityChen, H=rp00383en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1086/594374en_HK
dc.identifier.pmid19032063en_HK
dc.identifier.scopuseid_2-s2.0-58749101350en_HK
dc.identifier.hkuros163959-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-58749101350&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume199en_HK
dc.identifier.issue1en_HK
dc.identifier.spage49en_HK
dc.identifier.epage58en_HK
dc.identifier.isiWOS:000261754400008-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChen, Y=10739973700en_HK
dc.identifier.scopusauthoridQin, K=8512090900en_HK
dc.identifier.scopusauthoridWai, LW=23490386700en_HK
dc.identifier.scopusauthoridLi, G=37045135600en_HK
dc.identifier.scopusauthoridZhang, J=7601337832en_HK
dc.identifier.scopusauthoridDu, H=11940639200en_HK
dc.identifier.scopusauthoridMun, HN=26022536000en_HK
dc.identifier.scopusauthoridShih, JWK=7201812989en_HK
dc.identifier.scopusauthoridPeiris, JSM=7005486823en_HK
dc.identifier.scopusauthoridGuan, Y=7202924055en_HK
dc.identifier.scopusauthoridChen, H=26643315400en_HK
dc.identifier.scopusauthoridXia, N=35187953700en_HK
dc.identifier.citeulike3702994-
dc.customcontrol.immutablesml 130528-

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