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Tyrosine O-sulfation proteoforms affect HIV-1 monoclonal antibody potency

CAP256V2LS, a broadly neutralizing monoclonal antibody (bNAb), is being pursued as a promising drug for HIV-1 prevention. The total level of tyrosine-O-sulfation, a post-translational modification, was known to play a key role for antibody biological activity. More importantly, here wedescribe for t...

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Autores principales: Cai, Cindy X., Doria-Rose, Nicole A., Schneck, Nicole A., Ivleva, Vera B., Tippett, Brad, Shadrick, William R., O’Connell, Sarah, Cooper, Jonathan W., Schneiderman, Zachary, Zhang, Baoshan, Gowetski, Daniel B., Blackstock, Daniel, Demirji, Jacob, Lin, Bob C., Gorman, Jason, Liu, Tracy, Li, Yile, McDermott, Adrian B., Kwong, Peter D., Carlton, Kevin, Gall, Jason G., Lei, Q. Paula
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120178/
https://www.ncbi.nlm.nih.gov/pubmed/35589938
http://dx.doi.org/10.1038/s41598-022-12423-x
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author Cai, Cindy X.
Doria-Rose, Nicole A.
Schneck, Nicole A.
Ivleva, Vera B.
Tippett, Brad
Shadrick, William R.
O’Connell, Sarah
Cooper, Jonathan W.
Schneiderman, Zachary
Zhang, Baoshan
Gowetski, Daniel B.
Blackstock, Daniel
Demirji, Jacob
Lin, Bob C.
Gorman, Jason
Liu, Tracy
Li, Yile
McDermott, Adrian B.
Kwong, Peter D.
Carlton, Kevin
Gall, Jason G.
Lei, Q. Paula
author_facet Cai, Cindy X.
Doria-Rose, Nicole A.
Schneck, Nicole A.
Ivleva, Vera B.
Tippett, Brad
Shadrick, William R.
O’Connell, Sarah
Cooper, Jonathan W.
Schneiderman, Zachary
Zhang, Baoshan
Gowetski, Daniel B.
Blackstock, Daniel
Demirji, Jacob
Lin, Bob C.
Gorman, Jason
Liu, Tracy
Li, Yile
McDermott, Adrian B.
Kwong, Peter D.
Carlton, Kevin
Gall, Jason G.
Lei, Q. Paula
author_sort Cai, Cindy X.
collection PubMed
description CAP256V2LS, a broadly neutralizing monoclonal antibody (bNAb), is being pursued as a promising drug for HIV-1 prevention. The total level of tyrosine-O-sulfation, a post-translational modification, was known to play a key role for antibody biological activity. More importantly, here wedescribe for the first time the significance of the tyrosine-O-sulfation proteoforms. We developed a hydrophobic interaction chromatography (HIC) method to separate and quantify different sulfation proteoforms, which led to the direct functionality assessment of tyrosine-sulfated species. The fully sulfated (4-SO(3)) proteoform demonstrated the highest in vitro relative antigen binding potency and neutralization efficiency against a panel of HIV-1 viruses. Interestingly, highly variable levels of 4-SO(3) were produced by different clonal CHO cell lines, which helped the bNAb process development towards production of a highly potent CAP256V2LS clinical product with high 4-SO(3) proteoform. This study presents powerful insight for any biotherapeutic protein development where sulfation may play an important role in product efficacy.
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spelling pubmed-91201782022-05-21 Tyrosine O-sulfation proteoforms affect HIV-1 monoclonal antibody potency Cai, Cindy X. Doria-Rose, Nicole A. Schneck, Nicole A. Ivleva, Vera B. Tippett, Brad Shadrick, William R. O’Connell, Sarah Cooper, Jonathan W. Schneiderman, Zachary Zhang, Baoshan Gowetski, Daniel B. Blackstock, Daniel Demirji, Jacob Lin, Bob C. Gorman, Jason Liu, Tracy Li, Yile McDermott, Adrian B. Kwong, Peter D. Carlton, Kevin Gall, Jason G. Lei, Q. Paula Sci Rep Article CAP256V2LS, a broadly neutralizing monoclonal antibody (bNAb), is being pursued as a promising drug for HIV-1 prevention. The total level of tyrosine-O-sulfation, a post-translational modification, was known to play a key role for antibody biological activity. More importantly, here wedescribe for the first time the significance of the tyrosine-O-sulfation proteoforms. We developed a hydrophobic interaction chromatography (HIC) method to separate and quantify different sulfation proteoforms, which led to the direct functionality assessment of tyrosine-sulfated species. The fully sulfated (4-SO(3)) proteoform demonstrated the highest in vitro relative antigen binding potency and neutralization efficiency against a panel of HIV-1 viruses. Interestingly, highly variable levels of 4-SO(3) were produced by different clonal CHO cell lines, which helped the bNAb process development towards production of a highly potent CAP256V2LS clinical product with high 4-SO(3) proteoform. This study presents powerful insight for any biotherapeutic protein development where sulfation may play an important role in product efficacy. Nature Publishing Group UK 2022-05-19 /pmc/articles/PMC9120178/ /pubmed/35589938 http://dx.doi.org/10.1038/s41598-022-12423-x Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2022 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Cai, Cindy X.
Doria-Rose, Nicole A.
Schneck, Nicole A.
Ivleva, Vera B.
Tippett, Brad
Shadrick, William R.
O’Connell, Sarah
Cooper, Jonathan W.
Schneiderman, Zachary
Zhang, Baoshan
Gowetski, Daniel B.
Blackstock, Daniel
Demirji, Jacob
Lin, Bob C.
Gorman, Jason
Liu, Tracy
Li, Yile
McDermott, Adrian B.
Kwong, Peter D.
Carlton, Kevin
Gall, Jason G.
Lei, Q. Paula
Tyrosine O-sulfation proteoforms affect HIV-1 monoclonal antibody potency
title Tyrosine O-sulfation proteoforms affect HIV-1 monoclonal antibody potency
title_full Tyrosine O-sulfation proteoforms affect HIV-1 monoclonal antibody potency
title_fullStr Tyrosine O-sulfation proteoforms affect HIV-1 monoclonal antibody potency
title_full_unstemmed Tyrosine O-sulfation proteoforms affect HIV-1 monoclonal antibody potency
title_short Tyrosine O-sulfation proteoforms affect HIV-1 monoclonal antibody potency
title_sort tyrosine o-sulfation proteoforms affect hiv-1 monoclonal antibody potency
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120178/
https://www.ncbi.nlm.nih.gov/pubmed/35589938
http://dx.doi.org/10.1038/s41598-022-12423-x
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