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Potent and broad HIV-1 neutralization in fusion peptide-primed SHIV-infected macaques

  1. Author:
    Wang, Hua
    Cheng, Cheng
    Dal Santo, James L
    Shen, Chen-Hsiang
    Bylund, Tatsiana
    Henry, Amy R
    Howe, Colin A
    Hwang, Juyun
    Morano, Nicholas C
    Morris, Daniel J
    Pletnev, Sergei
    Roark, Ryan S
    Zhou, Tongqing
    Hansen, Bryan T
    Hoyt, Forrest H
    Johnston, Timothy S
    Wang, Shuyi
    Zhang, Baoshan
    Ambrozak, David R
    Becker, Jordan E
    Bender, Michael F
    Changela, Anita
    Chaudhary, Ridhi
    Corcoran, Martin
    Corrigan, Angela R
    Foulds, Kathryn E
    Guo, Yicheng
    Lee, Myungjin
    Li, Yingying
    Lin, Bob C
    Liu, Tracy
    Louder, Mark K
    Mandolesi, Marco
    Mason, Rosemarie D
    McKee, Krisha
    Nair, Vinod
    O'Dell, Sijy
    Olia, Adam S
    Ou, Li
    Pegu, Amarendra
    Raju, Nagarajan
    Rawi, Reda
    Roberts-Torres, Jesmine
    Sarfo, Edward K
    Sastry, Mallika
    Schaub, Andrew J
    Schmidt, Stephen D
    Schramm, Chaim A
    Schwartz, Cindi L
    Smith, Sarah C
    Stephens,Tyler
    Stuckey, Jonathan
    Teng, I-Ting
    Todd, John-Paul
    Tsybovsky,Yaroslav
    Van Wazer, David J
    Wang, Shuishu
    Doria-Rose, Nicole A
    Fischer, Elizabeth R
    Georgiev, Ivelin S
    Karlsson Hedestam, Gunilla B
    Sheng, Zizhang
    Woodward, Ruth A
    Douek, Daniel C
    Koup, Richard A
    Pierson, Theodore C
    Shapiro, Lawrence
    Shaw, George M
    Mascola, John R
    Kwong, Peter D

  2. Author Address

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Department of Biochemistry and Molecular Biophysics and Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA., Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Microscopy Unit, Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA., Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden., Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Vaccine Research Center Electron Microscopy Unit, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD 21702, USA., Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Modex Therapeutics Inc., Natick, MA 01760, USA., Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Biochemistry and Molecular Biophysics and Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA. Electronic address: pdkwong@nih.gov.,
    1. Year: 2024
    2. Date: Oct 23
    3. Epub Date: 2024 10 23
  2. Journal: Cell
  4. Type of Article: Article
  1. Abstract:

    An antibody-based HIV-1 vaccine will require the induction of potent cross-reactive HIV-1-neutralizing responses. To demonstrate feasibility toward this goal, we combined vaccination targeting the fusion-peptide site of vulnerability with infection by simian-human immunodeficiency virus (SHIV). In four macaques with vaccine-induced neutralizing responses, SHIV infection boosted plasma neutralization to 45%-77% breadth (geometric mean 50% inhibitory dilution [ID50] ~100) on a 208-strain panel. Molecular dissection of these responses by antibody isolation and cryo-electron microscopy (cryo-EM) structure determination revealed 15 of 16 antibody lineages with cross-clade neutralization to be directed toward the fusion-peptide site of vulnerability. In each macaque, isolated antibodies from memory B cells recapitulated the plasma-neutralizing response, with fusion-peptide-binding antibodies reaching breadths of 40%-60% (50% inhibitory concentration [IC50] < 50 µg/mL) and total lineage-concentrations estimates of 50-200 µg/mL. Longitudinal mapping indicated that these responses arose prior to SHIV infection. Collectively, these results provide in vivo molecular examples for one to a few B cell lineages affording potent, broadly neutralizing plasma responses. Published by Elsevier Inc.

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External Sources

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  2. DOI: 10.1016/j.cell.2024.10.003
  3. PMID: 39471811
  4. PII : S0092-8674(24)01151-6

Library Notes

  1. Fiscal Year: FY2024-2025
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