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VSV-Displayed HIV-1 Envelope Identifies Broadly Neutralizing Antibodies Class-Switched to IgG and IgA.
Jia, Manxue; Liberatore, Rachel A; Guo, Yicheng; Chan, Kun-Wei; Pan, Ruimin; Lu, Hong; Waltari, Eric; Mittler, Eva; Chandran, Kartik; Finzi, Andrés; Kaufmann, Daniel E; Seaman, Michael S; Ho, David D; Shapiro, Lawrence; Sheng, Zizhang; Kong, Xiang-Peng; Bieniasz, Paul D; Wu, Xueling.
Affiliation
  • Jia M; Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY 10016, USA.
  • Liberatore RA; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, New York, NY 10016, USA.
  • Guo Y; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
  • Chan KW; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
  • Pan R; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
  • Lu H; Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY 10016, USA.
  • Waltari E; Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY 10016, USA.
  • Mittler E; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • Chandran K; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • Finzi A; Centre de Recherche du CHUM and Université de Montréal, Montreal, QC H2X 0A9, Canada.
  • Kaufmann DE; Centre de Recherche du CHUM and Université de Montréal, Montreal, QC H2X 0A9, Canada; Center for HIV-1/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), La Jolla, CA 92037, USA.
  • Seaman MS; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
  • Ho DD; Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY 10016, USA.
  • Shapiro L; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bet
  • Sheng Z; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
  • Kong XP; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
  • Bieniasz PD; Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, New York, NY 10016, USA.
  • Wu X; Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY 10016, USA. Electronic address: xw2702@cumc.columbia.edu.
Cell Host Microbe ; 27(6): 963-975.e5, 2020 06 10.
Article in En | MEDLINE | ID: mdl-32315598
The HIV-1 envelope (Env) undergoes conformational changes during infection. Broadly neutralizing antibodies (bNAbs) are typically isolated by using soluble Env trimers, which do not capture all Env states. To address these limitations, we devised a vesicular stomatitis virus (VSV)-based probe to display membrane-embedded Env trimers and isolated five bNAbs from two chronically infected donors, M4008 and M1214. Donor B cell receptor (BCR) repertoires identified two bNAb lineages, M4008_N1 and M1214_N1, that class-switched to immunoglobulin G (IgG) and IgA. Variants of these bNAbs reconstituted as IgA demonstrated broadly neutralizing activity, and the IgA fraction of M1214 plasma conferred neutralization. M4008_N1 epitope mapping revealed a glycan-independent V3 epitope conferring tier 2 virus neutralization. A 4.86-Å-resolution cryogenic electron microscopy (cryo-EM) structure of M1214_N1 complexed with CH505 SOSIP revealed another elongated epitope, the V2V5 corridor, extending from V2 to V5. Overall, the VSVENV probe identified bNAb lineages with neutralizing IgG and IgA members targeting distinct sites of HIV-1 Env vulnerability.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Immunoglobulin A / Immunoglobulin G / HIV Antibodies / Env Gene Products, Human Immunodeficiency Virus / Broadly Neutralizing Antibodies / Viral Envelope Limits: Female / Humans Language: En Journal: Cell Host Microbe Journal subject: MICROBIOLOGIA Year: 2020 Document type: Article Affiliation country: Country of publication:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Immunoglobulin A / Immunoglobulin G / HIV Antibodies / Env Gene Products, Human Immunodeficiency Virus / Broadly Neutralizing Antibodies / Viral Envelope Limits: Female / Humans Language: En Journal: Cell Host Microbe Journal subject: MICROBIOLOGIA Year: 2020 Document type: Article Affiliation country: Country of publication: