Department of Pathology, Miller School of Medicine, University of Miami, Miami, Florida, USA.
AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Immunity. 2019 Mar 19;50(3):567-575.e5. doi: 10.1016/j.immuni.2019.02.005. Epub 2019 Mar 5.
Long-term delivery of anti-HIV monoclonal antibodies (mAbs) using adeno-associated virus (AAV) vectors holds promise for the prevention and treatment of HIV infection. We describe a therapy trial in which four rhesus monkeys were infected with SHIV-AD8 for 86 weeks before receiving the AAV-encoded mAbs 3BNC117, 10-1074, and 10E8. Although anti-drug antibody (ADA) responses restricted mAb delivery, one monkey successfully maintained 50-150 μg/mL of 3BNC117 and 10-1074 for over 2 years. Delivery of these two mAbs to this monkey resulted in an abrupt decline in plasma viremia, which remained undetectable for 38 successive measurements over 3 years. We generated two more examples of virologic suppression using AAV delivery of a cocktail of four mAbs in a 12-monkey study. Our results provide proof of concept for AAV-delivered mAbs to produce a "functional cure." However, they also serve as a warning that ADAs may be a problem for practical application of this approach in humans.
使用腺相关病毒 (AAV) 载体长期递呈抗 HIV 单克隆抗体 (mAb) 有望预防和治疗 HIV 感染。我们描述了一项治疗试验，其中四只恒河猴在感染 SHIV-AD8 86 周后接受了 AAV 编码的 mAb 3BNC117、10-1074 和 10E8。尽管抗药抗体 (ADA) 反应限制了 mAb 的递呈，但有一只猴子成功地将 3BNC117 和 10-1074 的浓度维持在 50-150μg/mL 超过 2 年。这只猴子接受这两种 mAb 的递呈后，血浆病毒载量迅速下降，在 3 年内连续 38 次检测均未检出。在一项包含 12 只猴子的研究中，我们使用 AAV 递呈四种 mAb 的鸡尾酒疗法产生了另外两个病毒学抑制的例子。我们的结果为 AAV 递呈 mAb 产生“功能性治愈”提供了概念验证。然而，它们也提醒人们，ADA 可能是该方法在人类实际应用中的一个问题。
