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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.
Affiliation
  • Cai CX; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • Doria-Rose NA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • Schneck NA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • Ivleva VB; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • Tippett B; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • Shadrick WR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • O'Connell S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • Cooper JW; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • Schneiderman Z; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • Zhang B; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • Gowetski DB; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • Blackstock D; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • Demirji J; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • Lin BC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • Gorman J; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • Liu T; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • Li Y; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • McDermott AB; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • Kwong PD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • Carlton K; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • Gall JG; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
  • Lei QP; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA. paula.lei@nih.gov.
Sci Rep ; 12(1): 8433, 2022 05 19.
Article in En | MEDLINE | ID: mdl-35589938
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV-1 Limits: Animals Language: En Journal: Sci Rep Year: 2022 Document type: Article Affiliation country: Estados Unidos
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV-1 Limits: Animals Language: En Journal: Sci Rep Year: 2022 Document type: Article Affiliation country: Estados Unidos