Search Menu
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information
Search Scholarly Publications

Title: Surface-Matrix Screening Identifies Semi-specific Interactions that Improve Potency of a Near Pan-reactive HIV-1-Neutralizing Antibody

Abstract

Highly effective HIV-1-neutralizing antibodies could have utility in the prevention or treatment of HIV-1 infection. To improve the potency of 10E8, an antibody capable of near pan-HIV-1 neutralization, we engineered 10E8-surface mutants and screened for improved neutralization. Variants with the largest functional enhancements involved the addition of hydrophobic or positively charged residues, which were positioned to interact with viral membrane lipids or viral glycan-sialic acids, respectively. In both cases, the site of improvement was spatially separated from the region of antibody mediating molecular contact with the protein component of the antigen, thereby improving peripheral semi-specific interactions while maintaining unmodified dominant contacts responsible for broad recognition. The optimized 10E8 antibody, with mutations to phenylalanine and arginine, retained the extraordinary breadth of 10E8 but with ~10-fold increased potency. We propose surface-matrix screening as a general method to improve antibodies, with improved semi-specific interactions between antibody and antigen enabling increased potency without compromising breadth.

Authors:
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; more »; ; ; ; ; ; ; ; ; ; ; ; ; « less
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH)
OSTI Identifier:
1630256
Alternate Identifier(s):
OSTI ID: 1464828
Grant/Contract Number:  
W-31-109-Eng-38
Resource Type:
Published Article
Journal Name:
Cell Reports
Additional Journal Information:
Journal Name: Cell Reports Journal Volume: 22 Journal Issue: 7; Journal ID: ISSN 2211-1247
Publisher:
Elsevier
Country of Publication:
Netherlands
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; antibody improvement; surface-matrix screening; HIV-1; broadly neutralizing antibody; membrane-proximal external region; MPER; 10E8

Citation Formats

Kwon, Young D., Chuang, Gwo-Yu, Zhang, Baoshan, Bailer, Robert T., Doria-Rose, Nicole A., Gindin, Tatyana S., Lin, Bob, Louder, Mark K., McKee, Krisha, O’Dell, Sijy, Pegu, Amarendra, Schmidt, Stephen D., Asokan, Mangaiarkarasi, Chen, Xuejun, Choe, Misook, Georgiev, Ivelin S., Jin, Vivian, Pancera, Marie, Rawi, Reda, Wang, Keyun, Chaudhuri, Rajoshi, Kueltzo, Lisa A., Manceva, Slobodanka D., Todd, John-Paul, Scorpio, Diana G., Kim, Mikyung, Reinherz, Ellis L., Wagh, Kshitij, Korber, Bette M., Connors, Mark, Shapiro, Lawrence, Mascola, John R., and Kwong, Peter D. Surface-Matrix Screening Identifies Semi-specific Interactions that Improve Potency of a Near Pan-reactive HIV-1-Neutralizing Antibody. Netherlands: N. p., 2018. Web. doi:10.1016/j.celrep.2018.01.023.
Copy to clipboard
Kwon, Young D., Chuang, Gwo-Yu, Zhang, Baoshan, Bailer, Robert T., Doria-Rose, Nicole A., Gindin, Tatyana S., Lin, Bob, Louder, Mark K., McKee, Krisha, O’Dell, Sijy, Pegu, Amarendra, Schmidt, Stephen D., Asokan, Mangaiarkarasi, Chen, Xuejun, Choe, Misook, Georgiev, Ivelin S., Jin, Vivian, Pancera, Marie, Rawi, Reda, Wang, Keyun, Chaudhuri, Rajoshi, Kueltzo, Lisa A., Manceva, Slobodanka D., Todd, John-Paul, Scorpio, Diana G., Kim, Mikyung, Reinherz, Ellis L., Wagh, Kshitij, Korber, Bette M., Connors, Mark, Shapiro, Lawrence, Mascola, John R., & Kwong, Peter D. Surface-Matrix Screening Identifies Semi-specific Interactions that Improve Potency of a Near Pan-reactive HIV-1-Neutralizing Antibody. Netherlands. https://doi.org/10.1016/j.celrep.2018.01.023
Copy to clipboard
Kwon, Young D., Chuang, Gwo-Yu, Zhang, Baoshan, Bailer, Robert T., Doria-Rose, Nicole A., Gindin, Tatyana S., Lin, Bob, Louder, Mark K., McKee, Krisha, O’Dell, Sijy, Pegu, Amarendra, Schmidt, Stephen D., Asokan, Mangaiarkarasi, Chen, Xuejun, Choe, Misook, Georgiev, Ivelin S., Jin, Vivian, Pancera, Marie, Rawi, Reda, Wang, Keyun, Chaudhuri, Rajoshi, Kueltzo, Lisa A., Manceva, Slobodanka D., Todd, John-Paul, Scorpio, Diana G., Kim, Mikyung, Reinherz, Ellis L., Wagh, Kshitij, Korber, Bette M., Connors, Mark, Shapiro, Lawrence, Mascola, John R., and Kwong, Peter D. Thu . "Surface-Matrix Screening Identifies Semi-specific Interactions that Improve Potency of a Near Pan-reactive HIV-1-Neutralizing Antibody". Netherlands. https://doi.org/10.1016/j.celrep.2018.01.023.
Copy to clipboard
@article{osti_1630256,
title = {Surface-Matrix Screening Identifies Semi-specific Interactions that Improve Potency of a Near Pan-reactive HIV-1-Neutralizing Antibody},
author = {Kwon, Young D. and Chuang, Gwo-Yu and Zhang, Baoshan and Bailer, Robert T. and Doria-Rose, Nicole A. and Gindin, Tatyana S. and Lin, Bob and Louder, Mark K. and McKee, Krisha and O’Dell, Sijy and Pegu, Amarendra and Schmidt, Stephen D. and Asokan, Mangaiarkarasi and Chen, Xuejun and Choe, Misook and Georgiev, Ivelin S. and Jin, Vivian and Pancera, Marie and Rawi, Reda and Wang, Keyun and Chaudhuri, Rajoshi and Kueltzo, Lisa A. and Manceva, Slobodanka D. and Todd, John-Paul and Scorpio, Diana G. and Kim, Mikyung and Reinherz, Ellis L. and Wagh, Kshitij and Korber, Bette M. and Connors, Mark and Shapiro, Lawrence and Mascola, John R. and Kwong, Peter D.},
abstractNote = {Highly effective HIV-1-neutralizing antibodies could have utility in the prevention or treatment of HIV-1 infection. To improve the potency of 10E8, an antibody capable of near pan-HIV-1 neutralization, we engineered 10E8-surface mutants and screened for improved neutralization. Variants with the largest functional enhancements involved the addition of hydrophobic or positively charged residues, which were positioned to interact with viral membrane lipids or viral glycan-sialic acids, respectively. In both cases, the site of improvement was spatially separated from the region of antibody mediating molecular contact with the protein component of the antigen, thereby improving peripheral semi-specific interactions while maintaining unmodified dominant contacts responsible for broad recognition. The optimized 10E8 antibody, with mutations to phenylalanine and arginine, retained the extraordinary breadth of 10E8 but with ~10-fold increased potency. We propose surface-matrix screening as a general method to improve antibodies, with improved semi-specific interactions between antibody and antigen enabling increased potency without compromising breadth.},
doi = {10.1016/j.celrep.2018.01.023},
journal = {Cell Reports},
number = 7,
volume = 22,
place = {Netherlands},
year = {Thu Feb 01 00:00:00 EST 2018},
month = {Thu Feb 01 00:00:00 EST 2018}
}
Copy to clipboard
Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1016/j.celrep.2018.01.023
Copyright Statement
Other availability
Search WorldCat Search WorldCat to find libraries that may hold this journal
Citation Metrics:
Cited by: 34 works
Citation information provided by
Web of Science
Save / Share:
Export Metadata
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.

Works referencing / citing this record:

Molecular recognition of the native HIV-1 MPER revealed by STED microscopy of single virions
journal, January 2019

An MPER antibody neutralizes HIV-1 using germline features shared among donors
journal, November 2019

Recent progress in broadly neutralizing antibodies to HIV
journal, October 2018

Rational design and in vivo selection of SHIVs encoding transmitted/founder subtype C HIV-1 envelopes
journal, April 2019

    Sort by:
    [ × clear filter / sort ]

    Similar Records in DOE PAGES and OSTI.GOV collections: