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Article: Humanized antibodies with broad-spectrum neutralization to avian influenza virus H5N1

TitleHumanized antibodies with broad-spectrum neutralization to avian influenza virus H5N1
Authors
Issue Date2010
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/antiviral
Citation
Antiviral Research, 2010, v. 87 n. 1, p. 81-84 How to Cite?
AbstractHemagglutinin (HA), the major antigen on the surface of influenza viruses, is the primary target for neutralizing antibodies and vaccine design. However, frequent mutations in this gene allow the virus to evade host immune responses and conventional prophylaxis and treatment. In this report, we humanized 4D1 and 10F7 mouse monoclonal antibodies (mAbs) that, we had previously shown to display broad-spectrum neutralization to avian H5N1 virus. The genes of variable (V) regions of 4D1 and 10F7 mAbs were combined with constant region of human antibody to construct the chimeric antibodies (cAbs). The results of hemagglutinin inhibition (HI) and neutralization assays showed that 4D1 and 10F7 cAbs were functional and retained broad-spectrum reactivity. Antibody competitive ELISA and affinity tests indicated that the cAbs recognized the same epitope as the parent mAbs with similar affinity. In animal experiments, the 10F7 cAb showed full protection against lethal challenge of highly virulent avian H5N1 virus, A/BH Goose/QH/15C/2005, in all infected mice. These humanized broad-spectrum antibodies may be potentially important for the control of both current and future antigenic variants of H5N1 virus. © 2010 Elsevier B.V.
Persistent Identifierhttp://hdl.handle.net/10722/125143
ISSN
2014 Impact Factor: 3.938
2014 SCImago Journal Rankings: 1.399
ISI Accession Number ID
Funding AgencyGrant Number
Science and Technology Foundation of Fujian Province2009YZ0002
Chinese Ministry of Education108157
National Natural Science Foundation of China30901077
Ministry of Health2008ZX10004-006
Area of Excellence Scheme of the UniversityA0E/M-12/06
Research Grants CouncilRGC 7619/07
research fund for the Control of Infectious Diseases of the Hong Kong SAR Government
Funding Information:

We acknowledge grants from the Key Project of the Science and Technology Foundation of Fujian Province (Grant No. 2009YZ0002), the Key Project of Chinese Ministry of Education (Grant No. 108157), and the National Natural Science Foundation of China (Grant No. 30901077), Key Project of Ministry of Health (Grant No. 2008ZX10004-006) the Area of Excellence Scheme of the University Grants (Grant A0E/M-12/06), the Research Grants Council (RGC 7619/07) and the research fund for the Control of Infectious Diseases of the Hong Kong SAR Government. We thank Dr. Kong T. Chong for helpful comments and critical review of this manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorChen, Yen_HK
dc.contributor.authorLuo, Wen_HK
dc.contributor.authorWu, WLen_HK
dc.contributor.authorFang, Zen_HK
dc.contributor.authorXia, Len_HK
dc.contributor.authorGui, Xen_HK
dc.contributor.authorChen, Yen_HK
dc.contributor.authorChen, Hen_HK
dc.contributor.authorShih, JWKen_HK
dc.contributor.authorXia, Nen_HK
dc.date.accessioned2010-10-31T11:13:50Z-
dc.date.available2010-10-31T11:13:50Z-
dc.date.issued2010en_HK
dc.identifier.citationAntiviral Research, 2010, v. 87 n. 1, p. 81-84en_HK
dc.identifier.issn0166-3542en_HK
dc.identifier.urihttp://hdl.handle.net/10722/125143-
dc.description.abstractHemagglutinin (HA), the major antigen on the surface of influenza viruses, is the primary target for neutralizing antibodies and vaccine design. However, frequent mutations in this gene allow the virus to evade host immune responses and conventional prophylaxis and treatment. In this report, we humanized 4D1 and 10F7 mouse monoclonal antibodies (mAbs) that, we had previously shown to display broad-spectrum neutralization to avian H5N1 virus. The genes of variable (V) regions of 4D1 and 10F7 mAbs were combined with constant region of human antibody to construct the chimeric antibodies (cAbs). The results of hemagglutinin inhibition (HI) and neutralization assays showed that 4D1 and 10F7 cAbs were functional and retained broad-spectrum reactivity. Antibody competitive ELISA and affinity tests indicated that the cAbs recognized the same epitope as the parent mAbs with similar affinity. In animal experiments, the 10F7 cAb showed full protection against lethal challenge of highly virulent avian H5N1 virus, A/BH Goose/QH/15C/2005, in all infected mice. These humanized broad-spectrum antibodies may be potentially important for the control of both current and future antigenic variants of H5N1 virus. © 2010 Elsevier B.V.en_HK
dc.languageengen_HK
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/antiviralen_HK
dc.relation.ispartofAntiviral Researchen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshAntibodies, Monoclonal - genetics - immunology - therapeutic useen_HK
dc.subject.meshAntibodies, Neutralizing - genetics - immunology - therapeutic useen_HK
dc.subject.meshAntibodies, Viral - genetics - immunology - therapeutic useen_HK
dc.subject.meshAntiviral Agents - immunology - therapeutic useen_HK
dc.subject.meshBody Weighten_HK
dc.subject.meshEpitope Mappingen_HK
dc.subject.meshHemagglutination Inhibition Testsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshImmunoglobulin Constant Regions - geneticsen_HK
dc.subject.meshImmunoglobulin Variable Region - geneticsen_HK
dc.subject.meshInfluenza A Virus, H5N1 Subtype - immunologyen_HK
dc.subject.meshInfluenza, Humanen_HK
dc.subject.meshMiceen_HK
dc.subject.meshNeutralization Testsen_HK
dc.subject.meshOrthomyxoviridae Infections - drug therapy - pathologyen_HK
dc.subject.meshSurvival Analysisen_HK
dc.titleHumanized antibodies with broad-spectrum neutralization to avian influenza virus H5N1en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0166-3542&volume=87&spage=81&epage=4&date=2010&atitle=Humanized+Antibodies+with+Broad-Spectrum+Neutralization+to+Avian+Influenza+Virus+H5N1en_HK
dc.identifier.emailChen, H:hlchen@hkucc.hku.hken_HK
dc.identifier.authorityChen, H=rp00383en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.antiviral.2010.04.012en_HK
dc.identifier.pmid20450935en_HK
dc.identifier.scopuseid_2-s2.0-77953535080en_HK
dc.identifier.hkuros180505en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77953535080&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume87en_HK
dc.identifier.issue1en_HK
dc.identifier.spage81en_HK
dc.identifier.epage84en_HK
dc.identifier.isiWOS:000279452800012-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridChen, Y=8705548300en_HK
dc.identifier.scopusauthoridLuo, W=7202199022en_HK
dc.identifier.scopusauthoridWu, WL=16835478800en_HK
dc.identifier.scopusauthoridFang, Z=36165347000en_HK
dc.identifier.scopusauthoridXia, L=36674086100en_HK
dc.identifier.scopusauthoridGui, X=36092830100en_HK
dc.identifier.scopusauthoridChen, Y=10739973700en_HK
dc.identifier.scopusauthoridChen, H=26643315400en_HK
dc.identifier.scopusauthoridShih, JWK=7201812989en_HK
dc.identifier.scopusauthoridXia, N=35187953700en_HK
dc.identifier.citeulike7152373-

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