TLR7 agonist, N6-LS and PGT121 delayed viral rebound in SHIV-infected macaques after antiretroviral therapy interruption

Denise C. Hsu, Alexandra Schuetz, Rawiwan Imerbsin, Decha Silsorn, Amarendra Pegu, Dutsadee Inthawong, Jumpol Sopanaporn, Pornsuk Visudhiphan, Weerawan Chuenarom, Boot Keawboon, Wei Shi, Merlin L. Robb, John R. Mascola, Romas Geleziunas, Richard A. Koup, Dan H. Barouch, Nelson L. Michael, Sandhya Vasan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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.

Original languageEnglish
Article numbere1009339
JournalPLoS Pathogens
Volume17
Issue number2
DOIs
StatePublished - 18 Feb 2021
Externally publishedYes

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