| Literature DB >> 33600506 |
Denise C Hsu1,2,3, Alexandra Schuetz1,2,3, Rawiwan Imerbsin1, Decha Silsorn1, Amarendra Pegu4, Dutsadee Inthawong1, Jumpol Sopanaporn1, Pornsuk Visudhiphan1, Weerawan Chuenarom1, Boot Keawboon1, Wei Shi4, Merlin L Robb2,3, John R Mascola4, Romas Geleziunas5, Richard A Koup4, Dan H Barouch6, Nelson L Michael7, Sandhya Vasan1,2,3.
Abstract
Toll-like receptor 7 (TLR7) agonist and PGT121 (broadly neutralizing antibody, bnAb) administration previously delayed viral rebound and induced SHIV remission. We evaluated the impact of GS-986 (TLR7 agonist) and dual bnAbs on viral rebound after antiretroviral therapy (ART) interruption. Rhesus macaques inoculated with SHIV-1157ipd3N4 were initiated on daily suppressive ART from Day 14 post SHIV inoculation. Active arm animals (n = 8) received GS-986, N6-LS and PGT121 after plasma viral suppression, starting from week 14. GS-986 induced immune activation and SHIV-specific T cell responses but not viral expression in all the active arm animals. After ART interruption, median time to viral rebound was 6 weeks in the active and 3 weeks in the control arm (p = 0.024). In this animal model, the administration of the combination of GS-986 and dual bnAbs was associated with a modest delay in viral rebound. This strategy should be further evaluated to better understand the underlying mechanisms for the induction of virus-specific immune responses and delay in viral rebound.Entities:
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Year: 2021 PMID： 33600506 PMCID： PMC7924766 DOI： 10.1371/journal.ppat.1009339
Source DB: PubMed Journal: PLoS Pathog ISSN： 1553-7366 Impact factor: 6.823