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Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding
Published on: September 15, 2010
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Tyrosine O-sulfation proteoforms affect HIV-1 monoclonal antibody potency
Cindy X Cai1, Nicole A Doria-Rose1, Nicole A Schneck1
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd, Gaithersburg, MD, 20878, USA.
Scientific Reports
|May 19, 2022
Summary
The study highlights tyrosine-O-sulfation proteoforms in the HIV-1 antibody CAP256V2LS. The fully sulfated form (4-SO3) shows superior binding and neutralization, guiding biotherapeutic development.
Area of Science:
- Biochemistry
- Immunology
- Biotechnology
Background:
- Tyrosine-O-sulfation is a critical post-translational modification influencing antibody function.
- Previous research established the general role of sulfation in antibody biological activity.
Purpose of the Study:
- To investigate the specific impact of different tyrosine-O-sulfation proteoforms on antibody efficacy.
- To develop a method for separating and assessing the functionality of these proteoforms.
Main Methods:
- Development of a hydrophobic interaction chromatography (HIC) method for proteoform separation and quantification.
- Direct assessment of the in vitro functionality of isolated tyrosine-sulfated species.
Main Results:
- The fully sulfated (4-SO3) proteoform of CAP256V2LS exhibited the highest antigen binding potency and HIV-1 neutralization efficiency.
- Significant variability in 4-SO3 proteoform levels was observed across different Chinese Hamster Ovary (CHO) cell lines.
- Process development enabled the production of a clinical-grade CAP256V2LS product enriched in the highly potent 4-SO3 proteoform.
Conclusions:
- Tyrosine-O-sulfation proteoforms, particularly the 4-SO3 form, are crucial for the efficacy of the broadly neutralizing antibody CAP256V2LS.
- The developed HIC method provides valuable insights for biotherapeutic protein development.
- Controlling sulfation proteoform levels is essential for producing potent therapeutic antibodies.
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