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

Cindy X. Cai; Nicole A. Doria-Rose; Nicole A. Schneck; Vera B. Ivleva; Brad Tippett; William R. Shadrick; Sarah O’Connell; Jonathan W. Cooper; Zachary Schneiderman; Baoshan Zhang; Daniel B. Gowetski; Daniel Blackstock; Jacob Demirji; Bob C. Lin; Jason Gorman; Tracy Liu; Yile Li; Adrian B. McDermott; Peter D. Kwong; Kevin Carlton; Jason G. Gall; Q. Paula Lei

doi:10.1038/s41598-022-12423-x

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

Cindy X. Cai, Nicole A. Doria-Rose, Nicole A. Schneck, Vera B. Ivleva, Brad Tippett, William R. Shadrick, Sarah O’Connell, Jonathan W. Cooper, Zachary Schneiderman, Baoshan Zhang, Daniel B. Gowetski, Daniel Blackstock, Jacob Demirji, Bob C. Lin, Jason Gorman, Tracy Liu, Yile Li, Adrian B. McDermott, Peter D. Kwong, Kevin CarltonJason G. Gall, Q. Paula Lei

National Institute of Allergy and Infectious Diseases (NIAID)

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

9 Citations (Scopus)

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.

Original language	English
Article number	8433
Journal	Scientific Reports
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41598-022-12423-x
Publication status	Published - Dec 2022
Externally published	Yes

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Cai, C. X., Doria-Rose, N. A., Schneck, N. A., Ivleva, V. B., Tippett, B., Shadrick, W. R., O’Connell, S., Cooper, J. W., Schneiderman, Z., Zhang, B., Gowetski, D. B., Blackstock, D., Demirji, J., Lin, B. C., Gorman, J., Liu, T., Li, Y., McDermott, A. B., Kwong, P. D., ... Lei, Q. P. (2022). Tyrosine O-sulfation proteoforms affect HIV-1 monoclonal antibody potency. Scientific Reports, 12(1), Article 8433. https://doi.org/10.1038/s41598-022-12423-x

@article{d56f383a924b43b4b5e2c4124e948764,

title = "Tyrosine O-sulfation proteoforms affect HIV-1 monoclonal antibody potency",

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.",

author = "Cai, \{Cindy X.\} and Doria-Rose, \{Nicole A.\} and Schneck, \{Nicole A.\} and Ivleva, \{Vera B.\} and Brad Tippett and Shadrick, \{William R.\} and Sarah O{\textquoteright}Connell and Cooper, \{Jonathan W.\} and Zachary Schneiderman and Baoshan Zhang and Gowetski, \{Daniel B.\} and Daniel Blackstock and Jacob Demirji and Lin, \{Bob C.\} and Jason Gorman and Tracy Liu and Yile Li and McDermott, \{Adrian B.\} and Kwong, \{Peter D.\} and Kevin Carlton and Gall, \{Jason G.\} and Lei, \{Q. Paula\}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41598-022-12423-x",

language = "English",

volume = "12",

journal = "Scientific Reports",

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Cai, CX, Doria-Rose, NA, Schneck, NA, Ivleva, VB, Tippett, B, Shadrick, WR, O’Connell, S, Cooper, JW, Schneiderman, Z, Zhang, B, Gowetski, DB, Blackstock, D, Demirji, J, Lin, BC, Gorman, J, Liu, T, Li, Y, McDermott, AB, Kwong, PD, Carlton, K, Gall, JG & Lei, QP 2022, 'Tyrosine O-sulfation proteoforms affect HIV-1 monoclonal antibody potency', Scientific Reports, vol. 12, no. 1, 8433. https://doi.org/10.1038/s41598-022-12423-x

TY - JOUR

T1 - Tyrosine O-sulfation proteoforms affect HIV-1 monoclonal antibody potency

AU - Cai, Cindy X.

AU - Doria-Rose, Nicole A.

AU - Schneck, Nicole A.

AU - Ivleva, Vera B.

AU - Tippett, Brad

AU - Shadrick, William R.

AU - O’Connell, Sarah

AU - Cooper, Jonathan W.

AU - Schneiderman, Zachary

AU - Zhang, Baoshan

AU - Gowetski, Daniel B.

AU - Blackstock, Daniel

AU - Demirji, Jacob

AU - Lin, Bob C.

AU - Gorman, Jason

AU - Liu, Tracy

AU - Li, Yile

AU - McDermott, Adrian B.

AU - Kwong, Peter D.

AU - Carlton, Kevin

AU - Gall, Jason G.

AU - Lei, Q. Paula

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85130344683

U2 - 10.1038/s41598-022-12423-x

DO - 10.1038/s41598-022-12423-x

M3 - Article

C2 - 35589938

AN - SCOPUS:85130344683

SN - 2045-2322

VL - 12

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 8433

ER -

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

Abstract

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