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- Title
Tyrosine O-sulfation proteoforms affect HIV-1 monoclonal antibody potency.
- Authors
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
- 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-SO3) 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-SO3 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-SO3 proteoform. This study presents powerful insight for any biotherapeutic protein development where sulfation may play an important role in product efficacy.
- Subjects
HIV; CHO cell; TYROSINE; SULFATION; HYDROPHOBIC interactions; POST-translational modification; MONOCLONAL antibodies
- Publication
Scientific Reports, 2022, Vol 12, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-022-12423-x