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dc.contributor.authorZheng, Q. B.zh_CN
dc.contributor.authorXia, L.zh_CN
dc.contributor.authorWu, W. L.zh_CN
dc.contributor.authorZheng, Z. H.zh_CN
dc.contributor.authorHuo, Y. T.zh_CN
dc.contributor.authorWu, J.zh_CN
dc.contributor.authorLiu, Y. N.zh_CN
dc.contributor.authorYu, H.zh_CN
dc.contributor.authorChen, Y. X.zh_CN
dc.contributor.authorLau, S. Y.zh_CN
dc.contributor.authorChen, H. L.zh_CN
dc.contributor.authorLuo, W. X.zh_CN
dc.contributor.authorXia, N. S.zh_CN
dc.contributor.author罗文新zh_CN
dc.date.accessioned2013-12-12T02:08:37Z
dc.date.available2013-12-12T02:08:37Z
dc.date.issued2011-04zh_CN
dc.identifier.citationAntimicrobial Agents and Chemotherapy, 2011,55(4):1349-1357zh_CN
dc.identifier.issn0066-4804zh_CN
dc.identifier.otherISI:000288594600004zh_CN
dc.identifier.urihttps://dspace.xmu.edu.cn/handle/2288/60644
dc.identifier.urihttp://dx.doi.org/10.1128/AAC.01436-10
dc.descriptionScience and Technology Foundation of Fujian Province [2009YZ0002]; National Natural Science Foundation of China [30901077]; Ministry of Health [2008ZX10004-006]; University Grants Committee [AoE/M-12/06]; National Institutes of Health [HHSN2662007 00005C]zh_CN
dc.description.abstractHighly pathogenic H5N1 virus infection causes severe disease and a high rate of fatality in humans. Development of humanized monoclonal antibodies may provide an efficient therapeutic regime for H5N1 virus infection. In the present study, broadly cross-reactive monoclonal antibodies (MAbs) derived from mice were humanized to minimize immunogenicity. One chimeric antibody (cAb) and seven humanized antibodies (hAbs) were constructed. These antibodies retained broad-spectrum reactivity to H5N1 viruses, binding to recombinant H5-subtype HA1 molecules expressed in CHO cells in a dose-dependent manner and exhibiting similar reactivities against antigenically distinct H5N1 viruses in hemagglutination inhibition (HI) assays. One humanized antibody, 37 hAb, showed HI and neutralization activities comparable to that of the parental murine antibody, 13D4 MAb, while the other six antibodies were less reactive to H5N1 viruses. Analysis of amino acid sequences in the variable region frameworks of the seven humanized antibodies found that Q5 and Y27 in the VH region are highly conserved murine residues. Comparison of the three-dimensional structures derived from the variable regions of MAbs 37 hAb, H1202-34, and 13D4 revealed that residue substitutions at sites 70 and 46 may be the major cause for the observed differences in binding affinity. Examination of the chimeric antibody and one of the humanized antibodies, 37 hAb, showed that both antibodies offered postinfection protection against lethal challenge with antigenically diverse H5N1 viruses in the mouse model. Chimeric and humanized antibodies which retain the broadly reactive and protective properties of murine H5-specific monoclonal antibodies have great potential for use in the treatment of human H5N1 infection.zh_CN
dc.language.isoen_USzh_CN
dc.source.urihttp://dx.doi.org/10.1128/AAC.01436-10zh_CN
dc.subjectOSELTAMIVIR-RESISTANT INFLUENZAzh_CN
dc.subjectA VIRUSzh_CN
dc.subjectINFECTIONzh_CN
dc.subjectTRANSMISSIONzh_CN
dc.subjectEPITOPEzh_CN
dc.subjectCHINAzh_CN
dc.subjectASIAzh_CN
dc.titleProperties and Therapeutic Efficacy of Broadly Reactive Chimeric and Humanized H5-Specific Monoclonal Antibodies against H5N1 Influenza Viruseszh_CN
dc.typeArticlezh_CN


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