Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
Nature. 2018 Nov;563(7731):360-364. doi: 10.1038/s41586-018-0600-6. Epub 2018 Oct 3.
The latent viral reservoir is the critical barrier for the development of a cure for HIV-1 infection. Previous studies have shown direct antiviral activity of potent HIV-1 Env-specific broadly neutralizing antibodies (bNAbs) administered when antiretroviral therapy (ART) was discontinued, but it remains unclear whether bNAbs can target the viral reservoir during ART. Here we show that administration of the V3 glycan-dependent bNAb PGT121 together with the Toll-like receptor 7 (TLR7) agonist vesatolimod (GS-9620) during ART delayed viral rebound following discontinuation of ART in simian-human immunodeficiency virus (SHIV)-SF162P3-infected rhesus monkeys in which ART was initiated during early acute infection. Moreover, in the subset of monkeys that were treated with both PGT121 and GS-9620 and that did not show viral rebound after discontinuation of ART, adoptive transfer studies and CD8-depletion studies also did not reveal virus. These data demonstrate the potential of bNAb administration together with innate immune stimulation as a possible strategy for targeting the viral reservoir.
潜伏的病毒库是开发 HIV-1 感染治愈方法的关键障碍。先前的研究表明，在停止抗逆转录病毒治疗（ART）时给予强效的 HIV-1 Env 特异性广谱中和抗体（bNAb）具有直接抗病毒活性，但尚不清楚 bNAb 是否可以在 ART 期间靶向病毒库。在这里，我们表明，在 simian-human immunodeficiency virus (SHIV)-SF162P3 感染的恒河猴中，在早期急性感染期间开始 ART 时，ART 期间同时给予 V3 聚糖依赖性 bNAb PGT121 和 Toll 样受体 7（TLR7）激动剂 vesatolimod（GS-9620），可延迟 ART 停止后病毒反弹。此外，在接受 PGT121 和 GS-9620 联合治疗且 ART 停止后未出现病毒反弹的猴子亚群中，过继转移研究和 CD8 耗竭研究也未发现病毒。这些数据表明，bNAb 给药联合先天免疫刺激可能是靶向病毒库的一种潜在策略。
