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Antibody-directed evolution reveals a mechanism for enhanced neutralization at the HIV-1 fusion peptide site
dc.contributor.author | Banach, Bailey B. | |
dc.contributor.author | Pletnev, Sergei | |
dc.contributor.author | Olia, Adam S. | |
dc.contributor.author | Xu, Kai | |
dc.contributor.author | Zhang, Baoshan | |
dc.contributor.author | Rawi, Reda | |
dc.contributor.author | Bylund, Tatsiana | |
dc.contributor.author | Doria-Rose, Nicole A. | |
dc.contributor.author | Nguyen, Thuy Duong | |
dc.contributor.author | Fahad, Ahmed S. | |
dc.contributor.author | Lee, Myungjin | |
dc.contributor.author | Lin, Bob C | |
dc.contributor.author | Liu, Tracy | |
dc.contributor.author | Louder, Mark K. | |
dc.contributor.author | Madan, Bharat | |
dc.contributor.author | McKee, Krisha | |
dc.contributor.author | O’Dell, Sijy | |
dc.contributor.author | Sastry, Mallika | |
dc.contributor.author | Schön, Arne | |
dc.contributor.author | Bui, Natalie | |
dc.contributor.author | Shen, Chen-Hsiang | |
dc.contributor.author | Wolfe, Jacy R. | |
dc.contributor.author | Chuang, Gwo-Yu | |
dc.contributor.author | Mascola, John R | |
dc.contributor.author | Kwong, Peter D. | |
dc.contributor.author | DeKosky, Brandon J. | |
dc.date.accessioned | 2024-06-17T18:59:58Z | |
dc.date.available | 2024-06-17T18:59:58Z | |
dc.date.issued | 2023-11-21 | |
dc.identifier.citation | Banach BB, Pletnev S, Olia AS, Xu K, Zhang B, Rawi R, Bylund T, Doria-Rose NA, Nguyen TD, Fahad AS, Lee M, Lin BC, Liu T, Louder MK, Madan B, McKee K, O'Dell S, Sastry M, Schön A, Bui N, Shen CH, Wolfe JR, Chuang GY, Mascola JR, Kwong PD, DeKosky BJ. Antibody-directed evolution reveals a mechanism for enhanced neutralization at the HIV-1 fusion peptide site. Nat Commun. 2023 Nov 21;14(1):7593. doi: 10.1038/s41467-023-42098-5. PMID: 37989731; PMCID: PMC10663459 | en_US |
dc.identifier.uri | https://hdl.handle.net/1808/35195 | |
dc.description.abstract | The HIV-1 fusion peptide (FP) represents a promising vaccine target, but global FP sequence diversity among circulating strains has limited anti-FP antibodies to ~60% neutralization breadth. Here we evolve the FP-targeting antibody VRC34.01 in vitro to enhance FP-neutralization using site saturation mutagenesis and yeast display. Successive rounds of directed evolution by iterative selection of antibodies for binding to resistant HIV-1 strains establish a variant, VRC34.01_mm28, as a best-in-class antibody with 10-fold enhanced potency compared to the template antibody and ~80% breadth on a cross-clade 208-strain neutralization panel. Structural analyses demonstrate that the improved paratope expands the FP binding groove to accommodate diverse FP sequences of different lengths while also recognizing the HIV-1 Env backbone. These data reveal critical antibody features for enhanced neutralization breadth and potency against the FP site of vulnerability and accelerate clinical development of broad HIV-1 FP-targeting vaccines and therapeutics. | en_US |
dc.publisher | Nature Research | en_US |
dc.rights | Copyright © The Author(s) 2023 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | HIV infections | en_US |
dc.subject | Molecular medicine | en_US |
dc.title | Antibody-directed evolution reveals a mechanism for enhanced neutralization at the HIV-1 fusion peptide site | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Nguyen, Thuy Duong | |
kusw.kuauthor | Fahad, Ahmed S. | |
kusw.kuauthor | Madan, Bharat | |
kusw.kuauthor | Bui, Natalie | |
kusw.kuauthor | Wolfe, Jacy R. | |
kusw.kuauthor | DeKosky, Brandon J. | |
kusw.kudepartment | Department of Pharmaceutical Chemistry | en_US |
kusw.kudepartment | Department of Chemical Engineering | en_US |
dc.identifier.doi | 10.1038/s41467-023-42098-5 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC10663459 | en_US |
dc.rights.accessrights | openAccess | en_US |
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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.