| Literature DB >> 27851912 |
Jinghe Huang1, Byong H Kang1, Elise Ishida1, Tongqing Zhou2, Trevor Griesman1, Zizhang Sheng3, Fan Wu4, Nicole A Doria-Rose2, Baoshan Zhang2, Krisha McKee2, Sijy O'Dell2, Gwo-Yu Chuang2, Aliaksandr Druz2, Ivelin S Georgiev5, Chaim A Schramm3, Anqi Zheng2, M Gordon Joyce2, Mangaiarkarasi Asokan2, Amy Ransier2, Sam Darko2, Stephen A Migueles1, Robert T Bailer2, Mark K Louder2, S Munir Alam6, Robert Parks6, Garnett Kelsoe6, Tarra Von Holle6, Barton F Haynes6, Daniel C Douek2, Vanessa Hirsch4, Michael S Seaman7, Lawrence Shapiro8, John R Mascola2, Peter D Kwong2, Mark Connors9.
Abstract
Detailed studies of the broadly neutralizing antibodies (bNAbs) that underlie the best available examples of the humoral immune response to HIV are providing important information for the development of therapies and prophylaxis for HIV-1 infection. Here, we report a CD4-binding site (CD4bs) antibody, named N6, that potently neutralized 98% of HIV-1 isolates, including 16 of 20 that were resistant to other members of its class. N6 evolved a mode of recognition such that its binding was not impacted by the loss of individual contacts across the immunoglobulin heavy chain. In addition, structural analysis revealed that the orientation of N6 permitted it to avoid steric clashes with glycans, which is a common mechanism of resistance. Thus, an HIV-1-specific bNAb can achieve potent, near-pan neutralization of HIV-1, making it an attractive candidate for use in therapy and prophylaxis. Published by Elsevier Inc.Entities:
Keywords: CD4-binding site; HIV; antibody; envelope; immunotherapy; neutralizing; prophylaxis; resistance; structure; vaccine
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Year: 2016 PMID： 27851912 PMCID： PMC5770152 DOI： 10.1016/j.immuni.2016.10.027
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745