國家衛生研究院 NHRI:Item 3990099045/11334
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    题名: Glycan-masking hemagglutinin antigens from stable CHO cell clones for H5N1 avian influenza vaccine development
    作者: Chen, TH;Liu, WC;Lin, CY;Liu, CC;Jan, JT;Spearman, M;Butler, M;Wu, SC
    贡献者: National Institute of Infectious Diseases and Vaccinology
    摘要: Refocusing of B cell responses can be achieved by preserving the overall fold of the antigen structure but selectively mutating the undesired antigenic sites with additional N-linked glycosylation motifs for glycan-masking the vaccine antigen. We previously reported that glycan-masking recombinant H5 hemagglutin (rH5HA) antigens on residues 83, 127, and 138 (g127+g138 or g83+g127+138 rH5HA) elicited broader neutralizing antibodies and protection against heterologous clades/subclades of high pathogenic avian influenza H5N1 viruses. In this study, we engineered the stably-expressing CHO cell clones for producing the glycan-masking g127+g138 and g83+g127+g138 rH5HA antigens. All of these glycan-masking rH5HA antigens produced in stable CHO cell clones were found to be mostly oligomeric structures. Only the immunization with the glycan-masking g127+g138 but not g83+g127+g138 rH5HA antigens elicited more potent neutralizing antibody titers against four out of five heterologous clades/subclades of H5N1 viral strains. The increased neutralizing antibody titers against these heterologous viral strains were correlated with the increased amounts of stem-binding antibodies, only the glycan-masking g127+g138 rH5HA antigens can translate into more protection against live viral challenges. The stable CHO cell line-produced glycan-masking g127+g138 rH5HA can be used for H5N1 subunit vaccine development.
    日期: 2019-03
    關聯: Biotechnology and Bioengineering. 2019 Mar;116(3):598-609.
    Link to: http://dx.doi.org/10.1002/bit.26810
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0006-3592&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000457802700012
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85059286242
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