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

Autor: Cale EM; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA., Bai H; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Bose M; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Messina MA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA., Colby DJ; SEARCH, Thai Red Cross Research Center, Bangkok, Thailand., Sanders-Buell E; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Dearlove B; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Li Y; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Engeman E; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Silas D; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., O'Sullivan AM; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Mann B; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Pinyakorn S; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Intasan J; SEARCH, Thai Red Cross Research Center, Bangkok, Thailand., Benjapornpong K; SEARCH, Thai Red Cross Research Center, Bangkok, Thailand., Sacdalan C; SEARCH, Thai Red Cross Research Center, Bangkok, Thailand., Kroon E; SEARCH, Thai Red Cross Research Center, Bangkok, Thailand., Phanuphak N; SEARCH, Thai Red Cross Research Center, Bangkok, Thailand., Gramzinski R; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Vasan S; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Robb ML; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Michael NL; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Lynch RM; George Washington University, Washington, DC, USA., Bailer RT; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA., Pagliuzza A; CHUM, Université de Montréal, Quebec, Canada., Chomont N; CHUM, Université de Montréal, Quebec, Canada., Pegu A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA., Doria-Rose NA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA., Trautmann L; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Crowell TA; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Mascola JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA., Ananworanich J; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA.; SEARCH, Thai Red Cross Research Center, Bangkok, Thailand.; Department of Global Health, University of Amsterdam, Amsterdam, Netherlands., Tovanabutra S; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA., Rolland M; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA.
Jazyk: angličtina
Zdroj: The Journal of clinical investigation [J Clin Invest] 2020 Jun 01; Vol. 130 (6), pp. 3299-3304.
DOI: 10.1172/JCI134395
Abstrakt: 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: MEDLINE