Neutralizing antibody VRC01 failed to select for HIV-1 mutations upon viral rebound
| Autor: | Yifan Li, Robert Gramzinski, Eugene Kroon, Donn J Colby, Sandhya Vasan, Nelson L. Michael, Carlo Sacdalan, Nicolas Chomont, John R. Mascola, Merlin L. Robb, Meera Bose, Evan M. Cale, Emily Engeman, Hongjun Bai, Nicole A. Doria-Rose, Eric Sanders-Buell, Nittaya Phanuphak, Rebecca M. Lynch, Daniel Silas, Robert T. Bailer, Brendan Mann, Jintanat Ananworanich, Anne Marie O'Sullivan, Bethany L. Dearlove, Sodsai Tovanabutra, Morgane Rolland, Lydie Trautmann, Trevor A Crowell, Amarendra Pegu, Khunthalee Benjapornpong, Suteeraporn Pinyakorn, Michael A. Messina, Amélie Pagliuzza, Jintana Intasan |
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| Přispěvatelé: | Graduate School, AII - Infectious diseases, APH - Aging & Later Life, Global Health |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Viral rebound Male Bioinformatics Adaptive immunity Viremia HIV Infections HIV Antibodies Epitope Neutralization AIDS/HIV 03 medical and health sciences Epitopes 0302 clinical medicine Medicine Humans Neutralizing antibody biology business.industry Concise Communication env Gene Products Human Immunodeficiency Virus General Medicine medicine.disease Acquired immune system Virology Antibodies Neutralizing 030104 developmental biology 030220 oncology & carcinogenesis Cohort Chronic Disease Mutation biology.protein HIV-1 Female Antibody business |
| Zdroj: | The Journal of Clinical Investigation Journal of clinical investigation, 130(6), 3299-3304. The American Society for Clinical Investigation |
| ISSN: | 1558-8238 0021-9738 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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