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Article: Humanized antibodies with broad-spectrum neutralization to avian influenza virus H5N1
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TitleHumanized antibodies with broad-spectrum neutralization to avian influenza virus H5N1
 
AuthorsChen, Y1
Luo, W1
Wu, WL2
Fang, Z1
Xia, L1
Gui, X1
Chen, Y1
Chen, H2
Shih, JWK1
Xia, N1
 
Issue Date2010
 
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/antiviral
 
CitationAntiviral Research, 2010, v. 87 n. 1, p. 81-84 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.antiviral.2010.04.012
 
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.
 
ISSN0166-3542
2012 Impact Factor: 3.925
2012 SCImago Journal Rankings: 1.169
 
DOIhttp://dx.doi.org/10.1016/j.antiviral.2010.04.012
 
ISI Accession Number IDWOS:000279452800012
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.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorChen, Y
 
dc.contributor.authorLuo, W
 
dc.contributor.authorWu, WL
 
dc.contributor.authorFang, Z
 
dc.contributor.authorXia, L
 
dc.contributor.authorGui, X
 
dc.contributor.authorChen, Y
 
dc.contributor.authorChen, H
 
dc.contributor.authorShih, JWK
 
dc.contributor.authorXia, N
 
dc.date.accessioned2010-10-31T11:13:50Z
 
dc.date.available2010-10-31T11:13:50Z
 
dc.date.issued2010
 
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.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationAntiviral Research, 2010, v. 87 n. 1, p. 81-84 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.antiviral.2010.04.012
 
dc.identifier.citeulike7152373
 
dc.identifier.doihttp://dx.doi.org/10.1016/j.antiviral.2010.04.012
 
dc.identifier.epage84
 
dc.identifier.hkuros180505
 
dc.identifier.isiWOS:000279452800012
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.

 
dc.identifier.issn0166-3542
2012 Impact Factor: 3.925
2012 SCImago Journal Rankings: 1.169
 
dc.identifier.issue1
 
dc.identifier.openurl
 
dc.identifier.pmid20450935
 
dc.identifier.scopuseid_2-s2.0-77953535080
 
dc.identifier.spage81
 
dc.identifier.urihttp://hdl.handle.net/10722/125143
 
dc.identifier.volume87
 
dc.languageeng
 
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/antiviral
 
dc.publisher.placeNetherlands
 
dc.relation.ispartofAntiviral Research
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAnimals
 
dc.subject.meshAntibodies, Monoclonal - genetics - immunology - therapeutic use
 
dc.subject.meshAntibodies, Neutralizing - genetics - immunology - therapeutic use
 
dc.subject.meshAntibodies, Viral - genetics - immunology - therapeutic use
 
dc.subject.meshAntiviral Agents - immunology - therapeutic use
 
dc.subject.meshBody Weight
 
dc.subject.meshEpitope Mapping
 
dc.subject.meshHemagglutination Inhibition Tests
 
dc.subject.meshHumans
 
dc.subject.meshImmunoglobulin Constant Regions - genetics
 
dc.subject.meshImmunoglobulin Variable Region - genetics
 
dc.subject.meshInfluenza A Virus, H5N1 Subtype - immunology
 
dc.subject.meshInfluenza, Human
 
dc.subject.meshMice
 
dc.subject.meshNeutralization Tests
 
dc.subject.meshOrthomyxoviridae Infections - drug therapy - pathology
 
dc.subject.meshSurvival Analysis
 
dc.titleHumanized antibodies with broad-spectrum neutralization to avian influenza virus H5N1
 
dc.typeArticle
 
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Author Affiliations
  1. Xiamen University
  2. The University of Hong Kong