In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-05-19)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-022-12423-x
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
2615211-3
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