Adeno-associated viral delivery of Env-specific antibodies prevents SIV rebound after discontinuing antiretroviral therapy.

Autor: Klenchin VA; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison; Madison, WI, 53705, USA., Clark NM; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison; Madison, WI, 53705, USA., Keles NK; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison; Madison, WI, 53705, USA., Capuano S; Wisconsin National Primate Research Center, University of Wisconsin-Madison; Madison, WI, 53715, USA., Mason R; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, MD, 20892, USA., Gao G; Deparment of Microbiology and Physiological Systems, University of Massachusetts Medical School; Worcester, MA, 01605, USA., Broman A; Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison; Madison, WI, 53705, USA., Kose E; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research; Frederick, MD, 21702, USA., Immonen TT; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research; Frederick, MD, 21702, USA., Fennessey CM; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research; Frederick, MD, 21702, USA., Keele BF; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research; Frederick, MD, 21702, USA., Lifson JD; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research; Frederick, MD, 21702, USA., Roederer M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, MD, 20892, USA., Gardner MR; Division of Infectious Diseases, Department of Medicine, Emory University; Atlanta, GA, 30329, USA.; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, 30329, USA., Evans DT; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison; Madison, WI, 53705, USA.; Wisconsin National Primate Research Center, University of Wisconsin-Madison; Madison, WI, 53715, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Jun 03. Date of Electronic Publication: 2024 Jun 03.
DOI: 10.1101/2024.05.30.593694
Abstrakt: An alternative to lifelong antiretroviral therapy (ART) is needed to achieve durable control of HIV-1. Here we show that adeno-associated virus (AAV)-delivery of two rhesus macaque antibodies to the SIV envelope glycoprotein (Env) with potent neutralization and antibody-dependent cellular cytotoxicity can prevent viral rebound in macaques infected with barcoded SIV mac 239M after discontinuing suppressive ART. Following AAV administration, sustained antibody expression with minimal anti-drug antibody responses was achieved in all but one animal. After ART withdrawal, SIV replication rebounded within two weeks in all of the control animals but remained below the threshold of detection in plasma (<15 copies/mL) for more than a year in four of the eight animals that received AAV vectors encoding Env-specific antibodies. Viral sequences from animals with delayed rebound exhibited restricted barcode diversity and antibody escape. Thus, sustained expression of antibodies with potent antiviral activity can afford durable, ART-free containment of pathogenic SIV infection.
Competing Interests: Competing interests Authors declare that they have no competing interests.
Databáze: MEDLINE
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