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Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys
Nature ( IF 50.5 ) Pub Date : 2018-10-03 , DOI: 10.1038/s41586-018-0600-6 Erica N Borducchi 1 , Jinyan Liu 1 , Joseph P Nkolola 1 , Anthony M Cadena 1 , Wen-Han Yu 2 , Stephanie Fischinger 2 , Thomas Broge 2 , Peter Abbink 1 , Noe B Mercado 1 , Abishek Chandrashekar 1 , David Jetton 1 , Lauren Peter 1 , Katherine McMahan 1 , Edward T Moseley 1 , Elena Bekerman 3 , Joseph Hesselgesser 3 , Wenjun Li 4 , Mark G Lewis 5 , Galit Alter 2 , Romas Geleziunas 3 , Dan H Barouch 1, 2
Nature ( IF 50.5 ) Pub Date : 2018-10-03 , DOI: 10.1038/s41586-018-0600-6 Erica N Borducchi 1 , Jinyan Liu 1 , Joseph P Nkolola 1 , Anthony M Cadena 1 , Wen-Han Yu 2 , Stephanie Fischinger 2 , Thomas Broge 2 , Peter Abbink 1 , Noe B Mercado 1 , Abishek Chandrashekar 1 , David Jetton 1 , Lauren Peter 1 , Katherine McMahan 1 , Edward T Moseley 1 , Elena Bekerman 3 , Joseph Hesselgesser 3 , Wenjun Li 4 , Mark G Lewis 5 , Galit Alter 2 , Romas Geleziunas 3 , Dan H Barouch 1, 2
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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.In monkeys infected with an AIDS-like virus, a combination of a broadly neutralizing antibody and an immune stimulator during antiretroviral therapy suppressed viral rebound after antiretroviral drug discontinuation.
中文翻译：
抗体和 TLR7 激动剂延缓 SHIV 感染猴子的病毒反弹
潜伏病毒库是开发治疗 HIV-1 感染的关键障碍。先前的研究表明，在停止抗逆转录病毒治疗 (ART) 时施用的有效 HIV-1 Env 特异性广泛中和抗体 (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，我们显示在 ART 期间施用 V3 聚糖依赖性 bNAb PGT121 和 Toll 样受体 7 (TLR7) 激动剂 vesatolimod (GS-9620) 可延缓猿猴-人类免疫缺陷病毒 (SHIV) 中停止 ART 后的病毒反弹 - SF162P3 感染的恒河猴，其中 ART 在早期急性感染期间开始。而且，在接受 PGT121 和 GS-9620 治疗且在停止 ART 后未显示病毒反弹的猴子亚组中，过继转移研究和 CD8 耗竭研究也未发现病毒。这些数据证明了 bNAb 给药和先天免疫刺激作为靶向病毒库的可能策略的潜力。在感染艾滋病样病毒的猴子中，在抗逆转录病毒治疗期间，广泛中和抗体和免疫刺激剂的组合抑制了病毒反弹抗逆转录病毒药物停药后。
更新日期：2018-10-03
中文翻译：
抗体和 TLR7 激动剂延缓 SHIV 感染猴子的病毒反弹
潜伏病毒库是开发治疗 HIV-1 感染的关键障碍。先前的研究表明，在停止抗逆转录病毒治疗 (ART) 时施用的有效 HIV-1 Env 特异性广泛中和抗体 (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，我们显示在 ART 期间施用 V3 聚糖依赖性 bNAb PGT121 和 Toll 样受体 7 (TLR7) 激动剂 vesatolimod (GS-9620) 可延缓猿猴-人类免疫缺陷病毒 (SHIV) 中停止 ART 后的病毒反弹 - SF162P3 感染的恒河猴，其中 ART 在早期急性感染期间开始。而且，在接受 PGT121 和 GS-9620 治疗且在停止 ART 后未显示病毒反弹的猴子亚组中，过继转移研究和 CD8 耗竭研究也未发现病毒。这些数据证明了 bNAb 给药和先天免疫刺激作为靶向病毒库的可能策略的潜力。在感染艾滋病样病毒的猴子中，在抗逆转录病毒治疗期间，广泛中和抗体和免疫刺激剂的组合抑制了病毒反弹抗逆转录病毒药物停药后。
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