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

biorxiv. 2024-06; 
Vadim A Klenchin, Natasha M Clark, Nida K Keles, Saverio Capuano, Rosemarie Mason, Guangping Gao, Aimee Broman, Emek Kose, Taina T Immonen, Christine M Fennessey, Brandon F Keele, Jeffrey D Lifson, Mario Roederer, Matthew R Gardner, David T Evans
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摘要

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 SIV239M 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 mo... More

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