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Virologic effects of broadly neutralizing antibodies VRC01LS and VRC07-523LS on chronic HIV-1 infection

  1. Author:
    Happe, Myra
    Lynch, Rebecca M
    Fichtenbaum, Carl J
    Heath, Sonya L
    Koletar, Susan L
    Landovitz, Raphael J
    Presti, Rachel M
    Santana-Bagur, Jorge L
    Tressler, Randall L
    Holman, LaSonji A
    Novik, Laura
    Roa, Jhoanna C
    Rothwell, Ro Shauna
    Strom, Larisa
    Wang,Jing
    Hu, Zonghui
    Conan-Cibotti, Michelle
    Bhatnagar, Anjali M
    Dwyer, Bridget
    Ko, Sung Hee
    Belinky, Frida
    Namboodiri, Aryan M
    Pandey, Janardan P
    Carroll, Robin
    Basappa, Manjula
    Serebryannyy, Leonid
    Narpala, Sandeep R
    Lin, Bob C
    McDermott, Adrian B
    Boritz, Eli A
    Capparelli, Edmund V
    Coates, Emily E
    Koup, Richard A
    Ledgerwood, Julie E
    Mascola, John R
    Chen, Grace L
    Tebas, Pablo

  2. Author Address

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA., Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, DC, USA., Division of Infectious Diseases, University of Cincinnati, Ohio, USA., Division of Infectious Diseases, University of Alabama, Birmingham, Alabama, USA., Division of Infectious Diseases, The Ohio State University, Columbus, Ohio, USA., Division of Infectious Diseases, David Geffen School of Medicine, UCLA, Los Angeles, California, USA., Division of Infectious Diseases, Washington University, St. Louis, Missouri, USA., School of Medicine, University of Puerto Rico, San Juan, Puerto Rico., Division of AIDS, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, USA., AIDS Network Coordinating Center, DLH Corporation, Bethesda, Maryland, USA., Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA., Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA., Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA., School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, UCSD, La Jolla, California, USA., Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.,
    1. Year: 2025
    2. Date: Feb 24
    3. Epub Date: 2025 02 24
  2. Journal: JCI Insight
    1. 10
    2. 4
  4. Type of Article: Article
  1. Abstract:

    BACKGROUNDHIV-1-specific broadly neutralizing monoclonal antibodies (bNAbs) have emerged as promising interventions with the potential to effectively treat and prevent HIV-1 infections. We conducted a phase I clinical trial evaluating the potent CD4-binding site-specific (CD4bs-specific) bNAbs VRC01LS and VRC07-523LS in people with HIV-1 (PWH) not receiving antiretroviral therapy (ART).METHODSParticipants received a single intravenous 40 mg/kg dose of either VRC01LS (n = 7) or VRC07-523LS (n = 9) and did not initiate ART for a minimum of 14 days. The primary study objective was to evaluate safety and tolerability; the secondary study objectives were to evaluate pharmacokinetics (PK) and the impact of administered bNAbs on viral loads (VL) and CD4+ T cell counts in the absence of ART.RESULTSThis trial enrolled 16 PWH aged 20 to 57 years. Both bNAbs were safe and well tolerated. Mild local reactogenicity was only reported in participants who received VRC07-523LS, while both bNAbs were associated with mild systemic symptoms. Maximum serum concentrations (Cmax) following VRC01LS or VRC07-523LS were 1,566 177; 316 and 1,295 177; 376 µg/mL, respectively. VRC07-523LS administration significantly decreased VL in 8 out of 9 participants, with an average decline of 1.7 177; 0.8 log10 copies/mL within 14 days after administration. In contrast, VRC01LS administration resulted in a smaller average decline (0.8 177; 0.8 log10 copies/mL), and 3 out of 7 participants showedno change in VL. Postinfusion maximum decline in VL correlated with post hoc baseline in vitro viral susceptibility results for both bNAbs.CONCLUSIONThe results of this trial support inclusion of potent CD4bs-specific bNAbs, such as VRC07-523LS, into next-generation treatment regimens for HIV-1.TRIAL REGISTRATIONClinicalTrials.gov NCT02840474.FUNDINGNational Institute of Allergy and Infectious Diseases (NIAID)/NIH (grants UM1 AI068634, UM1 AI068636, UM1 AI106701, UM1AI069424, UM1AI069501, UM1AI69415, UM1AI069534, UM1AI69494); the Intramural Research Program of the NIAID/NIH; National Center for Advancing Translational Sciences/NIH (grants UM1TR004548, UL1TR001881, and UL1TR001878); and the National Cancer Institute/NIH (contract 75N91019D00024).

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External Sources

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  2. DOI: 10.1172/jci.insight.181496
  3. PMID: 39989458
  4. PII : 181496

Library Notes

  1. Fiscal Year: FY2024-2025
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