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An MPER antibody neutralizes HIV-1 using germline features shared among donors.
Zhang, Lei; Irimia, Adriana; He, Lingling; Landais, Elise; Rantalainen, Kimmo; Leaman, Daniel P; Vollbrecht, Thomas; Stano, Armando; Sands, Daniel I; Kim, Arthur S; Poignard, Pascal; Burton, Dennis R; Murrell, Ben; Ward, Andrew B; Zhu, Jiang; Wilson, Ian A; Zwick, Michael B.
Afiliação
  • Zhang L; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, 92037, USA.
  • Irimia A; CTK Biotech, Inc., 3855 Stowe Drive, Poway, California, 92064, USA.
  • He L; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, 92037, USA.
  • Landais E; International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, California, 92037, USA.
  • Rantalainen K; Scripps Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, California, 92037, USA.
  • Leaman DP; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, 92037, USA.
  • Vollbrecht T; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, 92037, USA.
  • Stano A; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, 92037, USA.
  • Sands DI; International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, California, 92037, USA.
  • Kim AS; International AIDS Vaccine Initiative, New York, New York, 10004, USA.
  • Poignard P; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, 92037, USA.
  • Burton DR; Department of Medicine, University of California, San Diego, California, 92093, USA.
  • Murrell B; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, 92037, USA.
  • Ward AB; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, 92037, USA.
  • Zhu J; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, 92037, USA.
  • Wilson IA; Departments of Medicine, Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, 63110, USA.
Nat Commun ; 10(1): 5389, 2019 11 26.
Article em En | MEDLINE | ID: mdl-31772165
ABSTRACT
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteína gp41 do Envelope de HIV / HIV-1 / Anticorpos Neutralizantes Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteína gp41 do Envelope de HIV / HIV-1 / Anticorpos Neutralizantes Idioma: En Ano de publicação: 2019 Tipo de documento: Article