Surface-Matrix Screening Identifies Semi-specific Interactions that Improve Potency of a Near Pan-reactive HIV-1-Neutralizing Antibody
View/ Open
Author
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.
Wagh, Kshitij
Korber, Bette M.
Connors, Mark
Shapiro, Lawrence
Mascola, John R.
Kwong, Peter D.
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1016/j.celrep.2018.01.023Metadata
Show full item recordCitation
Kwon, Y. D., G. Chuang, B. Zhang, R. T. Bailer, N. A. Doria-Rose, T. S. Gindin, B. Lin, et al. 2018. “Surface-Matrix Screening Identifies Semi-specific Interactions that Improve Potency of a Near Pan-reactive HIV-1-Neutralizing Antibody.” Cell reports 22 (7): 1798-1809. doi:10.1016/j.celrep.2018.01.023. http://dx.doi.org/10.1016/j.celrep.2018.01.023.Abstract
SUMMARY 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889116/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:37067770
Collections
- HMS Scholarly Articles [17922]
Contact administrator regarding this item (to report mistakes or request changes)