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
2011 Impact Factor: 4.301
2011 SCImago Journal Rankings: 0.393
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 Field
Value
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
2011 Impact Factor: 4.301
2011 SCImago Journal Rankings: 0.393
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
Author Affiliations
  1. Xiamen University
  2. The University of Hong Kong