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

Lei Zhang ; Adriana Irimia ; Lingling He ; Elise Landais ; Kimmo Rantalainen ; Daniel P Leaman ; Thomas Vollbrecht ORCID logo ; Armando Stano ; Daniel I Sands ORCID logo ; Arthur S Kim ORCID logo ; +8 more... IAVI Protocol G Investigators ; Pascal Poignard ; Dennis R Burton ORCID logo ; Ben Murrell ; Andrew B Ward ORCID logo ; Jiang Zhu ; Ian A Wilson ORCID logo ; Michael B Zwick ; (2019) An MPER antibody neutralizes HIV-1 using germline features shared among donors. Nature communications, 10 (1). 5389-. ISSN 2041-1723 DOI: 10.1038/s41467-019-12973-1
Copy

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.


picture_as_pdf
Zhang-etal-2019-An-MPER-antibody-neutralizes-HIV-1-using-germline-features-shared-among-donors.pdf
subject
Published Version
Available under Creative Commons: Attribution 4.0

View Download

Atom BibTeX OpenURL ContextObject in Span Multiline CSV OpenURL ContextObject Dublin Core Dublin Core MPEG-21 DIDL Data Cite XML EndNote HTML Citation JSON MARC (ASCII) MARC (ISO 2709) METS MODS RDF+N3 RDF+N-Triples RDF+XML RIOXX2 XML Reference Manager Refer Simple Metadata ASCII Citation EP3 XML
Export

Downloads