Neutralizing antibody VRC01 failed to select for HIV-1 mutations upon viral rebound

Authors

Evan M. Cale, National Institute of Allergy and Infectious Diseases (NIAID)
Hongjun Bai, Walter Reed Army Institute of Research
Meera Bose, Walter Reed Army Institute of Research
Michael A. Messina, National Institute of Allergy and Infectious Diseases (NIAID)
Donn J. Colby, Thai Red Cross Agency
Eric Sanders-Buell, Walter Reed Army Institute of Research
Bethany Dearlove, Walter Reed Army Institute of Research
Yifan Li, Walter Reed Army Institute of Research
Emily Engeman, Walter Reed Army Institute of Research
Daniel Silas, Walter Reed Army Institute of Research
Anne Marie O'Sullivan, Walter Reed Army Institute of Research
Brendan Mann, Walter Reed Army Institute of Research
Suteeraporn Pinyakorn, Walter Reed Army Institute of Research
Jintana Intasan, Thai Red Cross Agency
Khunthalee Benjapornpong, Thai Red Cross Agency
Carlo Sacdalan, Thai Red Cross Agency
Eugène Kroon, Thai Red Cross Agency
Nittaya Phanuphak, Thai Red Cross Agency
Robert Gramzinski, Walter Reed Army Institute of Research
Sandhya Vasan, Walter Reed Army Institute of Research
Merlin L. Robb, Walter Reed Army Institute of Research
Nelson L. Michael, Walter Reed Army Institute of Research
Rebecca M. Lynch, The George Washington University
Robert T. Bailer, National Institute of Allergy and Infectious Diseases (NIAID)
Amélie Pagliuzza, University of Montreal
Nicolas Chomont, University of Montreal
Amarendra Pegu, National Institute of Allergy and Infectious Diseases (NIAID)
Nicole A. Doria-Rose, National Institute of Allergy and Infectious Diseases (NIAID)
Lydie Trautmann, Walter Reed Army Institute of Research
Trevor A. Crowell, Walter Reed Army Institute of Research
John R. Mascola, National Institute of Allergy and Infectious Diseases (NIAID)
Jintanat Ananworanich, Walter Reed Army Institute of Research

Document Type

Journal Article

Publication Date

6-1-2020

Journal

Journal of Clinical Investigation

Volume

130

Issue

6

DOI

10.1172/JCI134395

Abstract

Infusion of the broadly neutralizing antibody VRC01 has been evaluated in individuals chronically infected with HIV-1. Here, we studied how VRC01 infusions affected viral rebound after cessation of antiretroviral therapy (ART) in 18 acutely treated and durably suppressed individuals. Viral rebound occurred in all individuals, yet VRC01 infusions modestly delayed rebound and participants who showed a faster decay of VRC01 in serum rebounded more rapidly. Participants with strains most sensitive to VRC01 or with VRC01 epitope motifs similar to known VRC01-susceptible strains rebounded later. Upon rebound, HIV-1 sequences were indistinguishable from those sampled at diagnosis. Across the cohort, participant-derived Env showed different sensitivity to VRC01 neutralization (including 2 resistant viruses), yet neutralization sensitivity was similar at diagnosis and after rebound, indicating the lack of selection for VRC01 resistance during treatment interruption. Our results showed that viremia rebounded despite the absence of HIV-1 adaptation to VRC01 and an average VRC01 trough of 221 μg/mL. Although VRC01 levels were insufficient to prevent a resurgent infection, knowledge that they did not mediate Env mutations in acute-like viruses is relevant for antibody-based strategies in acute infection.

APA Citation

Cale, E., Bai, H., Bose, M., Messina, M., Colby, D., Sanders-Buell, E., Dearlove, B., Li, Y., Engeman, E., Silas, D., O'Sullivan, A., Mann, B., Pinyakorn, S., Intasan, J., Benjapornpong, K., Sacdalan, C., Kroon, E., Phanuphak, N., Gramzinski, R., Vasan, S., Robb, M., Michael, N., Lynch, R., Bailer, R., Pagliuzza, A., Chomont, N., Pegu, A., Doria-Rose, N., Trautmann, L., Crowell, T., Mascola, J., & Ananworanich, J. (2020). Neutralizing antibody VRC01 failed to select for HIV-1 mutations upon viral rebound. Journal of Clinical Investigation, 130 (6). http://dx.doi.org/10.1172/JCI134395