Cell Reports (Jul 2023)
HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide
- Shuishu Wang,
- Flavio Matassoli,
- Baoshan Zhang,
- Tracy Liu,
- Chen-Hsiang Shen,
- Tatsiana Bylund,
- Timothy Johnston,
- Amy R. Henry,
- I-Ting Teng,
- Prabhanshu Tripathi,
- Jordan E. Becker,
- Anita Changela,
- Ridhi Chaudhary,
- Cheng Cheng,
- Martin Gaudinski,
- Jason Gorman,
- Darcy R. Harris,
- Myungjin Lee,
- Nicholas C. Morano,
- Laura Novik,
- Sijy O’Dell,
- Adam S. Olia,
- Danealle K. Parchment,
- Reda Rawi,
- Jesmine Roberts-Torres,
- Tyler Stephens,
- Yaroslav Tsybovsky,
- Danyi Wang,
- David J. Van Wazer,
- Tongqing Zhou,
- Nicole A. Doria-Rose,
- Richard A. Koup,
- Lawrence Shapiro,
- Daniel C. Douek,
- Adrian B. McDermott,
- Peter D. Kwong
Affiliations
- Shuishu Wang
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Flavio Matassoli
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Baoshan Zhang
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Tracy Liu
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Chen-Hsiang Shen
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Tatsiana Bylund
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Timothy Johnston
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Amy R. Henry
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- I-Ting Teng
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Prabhanshu Tripathi
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Jordan E. Becker
- Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
- Anita Changela
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Ridhi Chaudhary
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Cheng Cheng
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Martin Gaudinski
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Jason Gorman
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Darcy R. Harris
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Myungjin Lee
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Nicholas C. Morano
- Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
- Laura Novik
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Sijy O’Dell
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Adam S. Olia
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Danealle K. Parchment
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Reda Rawi
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Jesmine Roberts-Torres
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Tyler Stephens
- Electron Microscopy Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA
- Yaroslav Tsybovsky
- Electron Microscopy Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA
- Danyi Wang
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- David J. Van Wazer
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Tongqing Zhou
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Nicole A. Doria-Rose
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Richard A. Koup
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Lawrence Shapiro
- Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
- Daniel C. Douek
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Adrian B. McDermott
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA
- Peter D. Kwong
- Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA; Department of Biochemistry and Molecular Biophysics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA; Corresponding author
- Journal volume & issue
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Vol. 42,
no. 7
p. 112755
Abstract
Summary: Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers eliciting autologous neutralizing antibodies has been reported in multiple vaccine-test species, though not in humans. To investigate elicitation of HIV-1 neutralizing antibodies in humans, here, we analyze B cells from a phase I clinical trial of the “DS-SOSIP”-stabilized envelope trimer from strain BG505, identifying two antibodies, N751-2C06.01 and N751-2C09.01 (named for donor-lineage.clone), that neutralize the autologous tier-2 strain, BG505. Though derived from distinct lineages, these antibodies form a reproducible antibody class that targets the HIV-1 fusion peptide. Both antibodies are highly strain specific, which we attribute to their partial recognition of a BG505-specific glycan hole and to their binding requirements for a few BG505-specific residues. Prefusion-stabilized envelope trimers can thus elicit autologous tier-2 neutralizing antibodies in humans, with initially identified neutralizing antibodies recognizing the fusion-peptide site of vulnerability.
