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Title: An MPER antibody neutralizes HIV-1 using germline features shared among donors
Authors: Lei Zhang
Adriana Irimia
Lingling He
Elise Landais
Kimmo Rantalainen
Daniel P. Leaman
Thomas Vollbrecht
Armando Stano
Daniel I. Sands
Arthur S. Kim
George Miiro
Jennifer Serwanga
Anton Pozniak
Dale McPhee
Oliver Manigart
Lawrence Mwananyanda
Etienne Karita
André Inwoley
Walter Jaoko
Jack DeHovitz
Linda Gail Bekker
Punnee Pitisuttithum
Robert Paris
Susan Allen
Pascal Poignard
Dennis R. Burton
Ben Murrell
Andrew B. Ward
Jiang Zhu
Ian A. Wilson
Michael B. Zwick
Universite Grenoble Alpes
International AIDS Vaccine Initiative
Centre Hospitalier Universitaire de Treichville
Uganda Virus Research Institute
University of Nairobi
University of California, San Diego
NHS Foundation Trust
SUNY Downstate Medical Center
Washington University School of Medicine in St. Louis
Massachusetts Institute of Technology
Karolinska University Hospital
Armed Forces Research Institute of Medical Sciences, Thailand
Mahidol University
Scripps Research Institute
Emory University
University of Cape Town
CTK Biotech, Inc.
Keywords: Biochemistry, Genetics and Molecular Biology;Chemistry
Issue Date: 1-Dec-2019
Citation: Nature Communications. Vol.10, No.1 (2019)
Abstract: © 2019, The Author(s). The membrane-proximal external region (MPER) of HIV-1 envelope glycoprotein (Env) can be targeted by neutralizing antibodies of exceptional breadth. MPER antibodies usually have long, hydrophobic CDRH3s, lack activity as inferred germline precursors, are often from the minor IgG3 subclass, and some are polyreactive, such as 4E10. Here we describe an MPER broadly neutralizing antibody from the major IgG1 subclass, PGZL1, which shares germline V/D-region genes with 4E10, has a shorter CDRH3, and is less polyreactive. A recombinant sublineage variant pan-neutralizes a 130-isolate panel at 1.4 μg/ml (IC50). Notably, a germline revertant with mature CDR3s neutralizes 12% of viruses and still binds MPER after DJ reversion. Crystal structures of lipid-bound PGZL1 variants and cryo-EM reconstruction of an Env-PGZL1 complex reveal how these antibodies recognize MPER and viral membrane. Discovery of common genetic and structural elements among MPER antibodies from different patients suggests that such antibodies could be elicited using carefully designed immunogens.
ISSN: 20411723
Appears in Collections:Scopus 2019

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