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TLR7 激动剂、N6-LS 和 PGT121 在抗逆转录病毒治疗中断后延缓了 SHIV 感染的猕猴体内的病毒反弹。

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

机构信息

Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.

出版信息

PLoS Pathog. 2021 Feb 18;17(2):e1009339. doi: 10.1371/journal.ppat.1009339. eCollection 2021 Feb.

DOI:10.1371/journal.ppat.1009339
PMID:33600506
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7924766/
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.

摘要

Toll 样受体 7（TLR7）激动剂和 PGT121（广泛中和抗体，bnAb）给药先前可延迟病毒反弹并诱导 SHIV 缓解。我们评估了 GS-986（TLR7 激动剂）和双 bnAb 对中断抗逆转录病毒治疗（ART）后病毒反弹的影响。用 SHIV-1157ipd3N4 接种恒河猴的动物从 SHIV 接种后第 14 天开始每天接受抑制性 ART。在血浆病毒抑制后，主动治疗组（n=8）的动物从第 14 周开始接受 GS-986、N6-LS 和 PGT121。GS-986 诱导了所有主动治疗组动物的免疫激活和 SHIV 特异性 T 细胞反应，但未诱导病毒表达。在 ART 中断后，主动治疗组和对照组的病毒反弹中位时间分别为 6 周和 3 周（p=0.024）。在这个动物模型中，联合使用 GS-986 和双 bnAb 可适度延迟病毒反弹。应进一步评估该策略，以更好地了解诱导病毒特异性免疫反应和延迟病毒反弹的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5c7/7924766/6950e5d15b35/ppat.1009339.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5c7/7924766/93fe71848436/ppat.1009339.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5c7/7924766/31ceef56aff2/ppat.1009339.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5c7/7924766/c7f3b8ee0f20/ppat.1009339.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5c7/7924766/5bdb8edc46e7/ppat.1009339.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5c7/7924766/8561e39354b3/ppat.1009339.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5c7/7924766/827df651ac14/ppat.1009339.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5c7/7924766/e7b0b557b4f4/ppat.1009339.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5c7/7924766/6950e5d15b35/ppat.1009339.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5c7/7924766/93fe71848436/ppat.1009339.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5c7/7924766/31ceef56aff2/ppat.1009339.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5c7/7924766/c7f3b8ee0f20/ppat.1009339.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5c7/7924766/5bdb8edc46e7/ppat.1009339.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5c7/7924766/8561e39354b3/ppat.1009339.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5c7/7924766/827df651ac14/ppat.1009339.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5c7/7924766/e7b0b557b4f4/ppat.1009339.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5c7/7924766/6950e5d15b35/ppat.1009339.g008.jpg

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