Adeno-associated viral delivery of Env-specific antibodies prevents SIV rebound after discontinuing antiretroviral therapy [preprint]
Klenchin, Vadim A ; Clark, Natasha M ; Keles, Nida K ; Capuano, Saverio ; Mason, Rosemarie ; Gao, Guangping ; Broman, Aimee ; Kose, Emek ; Immonen, Taina T ; Fennessey, Christine M ... show 5 more
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Abstract
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 SIVmac239M 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.
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Klenchin VA, Clark NM, Keles NK, Capuano S, Mason R, Gao G, Broman A, Kose E, Immonen TT, Fennessey CM, Keele BF, Lifson JD, Roederer M, Gardner MR, Evans DT. Adeno-associated viral delivery of Env-specific antibodies prevents SIV rebound after discontinuing antiretroviral therapy. bioRxiv [Preprint]. 2024 Jun 3:2024.05.30.593694. doi: 10.1101/2024.05.30.593694. PMID: 38895320; PMCID: PMC11185534.
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This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.