tetano
Editor, Senior Moderator
Biotechnol Bioeng. 2018 Aug 6. doi: 10.1002/bit.26810. [Epub ahead of print]
[h=1]Glycan-masking hemagglutinin antigens from stable CHO cell clones for H5N1 avian influenza vaccine development.[/h] Chen TH[SUP]1[/SUP], Liu WC[SUP]1[/SUP], Lin CY[SUP]1[/SUP], Liu CC[SUP]2[/SUP], Jan JT[SUP]3[/SUP], Spearman M[SUP]4[/SUP], Butler M[SUP]4[/SUP], Wu SC[SUP]1,[/SUP][SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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. This article is protected by copyright. All rights reserved.
[h=4]KEYWORDS:[/h] CHO cells; H5N1 vaccine; glycan-masking; hemagglutinin
PMID: 30080931 DOI: 10.1002/bit.26810
[h=1]Glycan-masking hemagglutinin antigens from stable CHO cell clones for H5N1 avian influenza vaccine development.[/h] Chen TH[SUP]1[/SUP], Liu WC[SUP]1[/SUP], Lin CY[SUP]1[/SUP], Liu CC[SUP]2[/SUP], Jan JT[SUP]3[/SUP], Spearman M[SUP]4[/SUP], Butler M[SUP]4[/SUP], Wu SC[SUP]1,[/SUP][SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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. This article is protected by copyright. All rights reserved.
[h=4]KEYWORDS:[/h] CHO cells; H5N1 vaccine; glycan-masking; hemagglutinin
PMID: 30080931 DOI: 10.1002/bit.26810