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

Myra Happe, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Rebecca M. Lynch, Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, DC, USA.
Carl J. Fichtenbaum, Division of Infectious Diseases, University of Cincinnati, Ohio, USA.
Sonya L. Heath, Division of Infectious Diseases, University of Alabama, Birmingham, Alabama, USA.
Susan L. Koletar, Division of Infectious Diseases, The Ohio State University, Columbus, Ohio, USA.
Raphael J. Landovitz, Division of Infectious Diseases, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Rachel M. Presti, Division of Infectious Diseases, Washington University, St. Louis, Missouri, USA.
Jorge L. Santana-Bagur, School of Medicine, University of Puerto Rico, San Juan, Puerto Rico.
Randall L. Tressler, Division of AIDS, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, USA.
LaSonji A. Holman, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Laura Novik, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Jhoanna C. Roa, AIDS Network Coordinating Center, DLH Corporation, Bethesda, Maryland, USA.
Ro Shauna Rothwell, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Larisa Strom, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Jing Wang, Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Zonghui Hu, Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Michelle Conan-Cibotti, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Anjali M. Bhatnagar, Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, DC, USA.
Bridget Dwyer, Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, DC, USA.
Sung Hee Ko, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Frida Belinky, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Aryan M. Namboodiri, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA.
Janardan P. Pandey, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA.
Robin Carroll, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Manjula Basappa, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Leonid Serebryannyy, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Sandeep R. Narpala, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Bob C. Lin, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Adrian B. McDermott, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Eli A. Boritz, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Edmund V. Capparelli, School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, UCSD, La Jolla, California, USA.
Emily E. Coates, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.

Document Type

Journal Article

Publication Date

2-24-2025

Journal

JCI insight

Volume

10

Issue

4

DOI

10.1172/jci.insight.181496

Keywords

AIDS/HIV; Clinical trials; Drug therapy

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 ± 316 and 1,295 ± 376 μg/mL, respectively. VRC07-523LS administration significantly decreased VL in 8 out of 9 participants, with an average decline of 1.7 ± 0.8 log10 copies/mL within 14 days after administration. In contrast, VRC01LS administration resulted in a smaller average decline (0.8 ± 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).

Department

Microbiology, Immunology, and Tropical Medicine

Link to Full Text

Share

COinS