Deglycosylation of eukaryotic-expressed flagellin restores adjuvanticity

Flagellin, the TLR5 agonist, shows potent adjuvant activities in diverse vaccines and immunotherapies. Vibrio vulnificus flagellin B expressed in eukaryotic cells (eFlaB) could not stimulate TLR5 signaling. Enzymatic deglycosylation restored eFlaB’s TLR5 stimulating functionality, suggesting that gl...

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Autores principales: Khim, Koemchhoy, Puth, Sao, Radhakrishnan, Kamalakannan, Nguyen, Tien Duc, Lee, Youn Suhk, Jung, Che-Hun, Lee, Shee Eun, Rhee, Joon Haeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Brief Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10522637/
https://www.ncbi.nlm.nih.gov/pubmed/37752138
http://dx.doi.org/10.1038/s41541-023-00738-3
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author Khim, Koemchhoy
Puth, Sao
Radhakrishnan, Kamalakannan
Nguyen, Tien Duc
Lee, Youn Suhk
Jung, Che-Hun
Lee, Shee Eun
Rhee, Joon Haeng
author_facet Khim, Koemchhoy
Puth, Sao
Radhakrishnan, Kamalakannan
Nguyen, Tien Duc
Lee, Youn Suhk
Jung, Che-Hun
Lee, Shee Eun
Rhee, Joon Haeng
author_sort Khim, Koemchhoy
collection PubMed
description Flagellin, the TLR5 agonist, shows potent adjuvant activities in diverse vaccines and immunotherapies. Vibrio vulnificus flagellin B expressed in eukaryotic cells (eFlaB) could not stimulate TLR5 signaling. Enzymatic deglycosylation restored eFlaB’s TLR5 stimulating functionality, suggesting that glycosylation interferes with eFlaB binding to TLR5. Site-directed mutagenesis of N-glycosylation residues restored TLR5 stimulation and adjuvanticity. Collectively, deglycosylated eFlaB may provide a built-in adjuvant platform for eukaryotic-expressed antigens and nucleic acid vaccines.
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spelling pubmed-105226372023-09-28 Deglycosylation of eukaryotic-expressed flagellin restores adjuvanticity Khim, Koemchhoy Puth, Sao Radhakrishnan, Kamalakannan Nguyen, Tien Duc Lee, Youn Suhk Jung, Che-Hun Lee, Shee Eun Rhee, Joon Haeng NPJ Vaccines Brief Communication Flagellin, the TLR5 agonist, shows potent adjuvant activities in diverse vaccines and immunotherapies. Vibrio vulnificus flagellin B expressed in eukaryotic cells (eFlaB) could not stimulate TLR5 signaling. Enzymatic deglycosylation restored eFlaB’s TLR5 stimulating functionality, suggesting that glycosylation interferes with eFlaB binding to TLR5. Site-directed mutagenesis of N-glycosylation residues restored TLR5 stimulation and adjuvanticity. Collectively, deglycosylated eFlaB may provide a built-in adjuvant platform for eukaryotic-expressed antigens and nucleic acid vaccines. Nature Publishing Group UK 2023-09-26 /pmc/articles/PMC10522637/ /pubmed/37752138 http://dx.doi.org/10.1038/s41541-023-00738-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Brief Communication
Khim, Koemchhoy
Puth, Sao
Radhakrishnan, Kamalakannan
Nguyen, Tien Duc
Lee, Youn Suhk
Jung, Che-Hun
Lee, Shee Eun
Rhee, Joon Haeng
Deglycosylation of eukaryotic-expressed flagellin restores adjuvanticity
title Deglycosylation of eukaryotic-expressed flagellin restores adjuvanticity
title_full Deglycosylation of eukaryotic-expressed flagellin restores adjuvanticity
title_fullStr Deglycosylation of eukaryotic-expressed flagellin restores adjuvanticity
title_full_unstemmed Deglycosylation of eukaryotic-expressed flagellin restores adjuvanticity
title_short Deglycosylation of eukaryotic-expressed flagellin restores adjuvanticity
title_sort deglycosylation of eukaryotic-expressed flagellin restores adjuvanticity
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10522637/
https://www.ncbi.nlm.nih.gov/pubmed/37752138
http://dx.doi.org/10.1038/s41541-023-00738-3
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