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Glycan‐masking hemagglutinin antigens from stable CHO cell clones for H5N1 avian influenza vaccine development
Author(s) -
Chen TingHsuan,
Liu WenChun,
Lin ChiaYing,
Liu ChiaChyi,
Jan JiaTsrong,
Spearman Maureen,
Butler Michael,
Wu SuhChin
Publication year - 2019
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.26810
Subject(s) - biology , virology , heterologous , glycan , chinese hamster ovary cell , antigen , hemagglutinin (influenza) , influenza a virus subtype h5n1 , glycosylation , antibody , influenza vaccine , microbiology and biotechnology , vaccination , glycoprotein , cell culture , immunology , genetics , virus , gene
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 hemagglutinin (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 Chinese hamster ovary (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.