Publication:
An MPER antibody neutralizes HIV-1 using germline features shared among donors

Issued Date

2019-12-01

Resource Type

Article

ISSN

20411723

DOI

10.1038/s41467-019-12973-1

Other identifier(s)

2-s2.0-85075605452

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Nature Communications. Vol.10, No.1 (2019)

Suggested Citation

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 An MPER antibody neutralizes HIV-1 using germline features shared among donors. Nature Communications. Vol.10, No.1 (2019). doi:10.1038/s41467-019-12973-1 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/50026

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Title

An MPER antibody neutralizes HIV-1 using germline features shared among donors

Author(s)

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

Other Contributor(s)

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.
 NRL

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.

Keyword(s)

Biochemistry, Genetics and Molecular Biology
 Chemistry

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/50026

Collections

Scopus 2019