An IL-15 superagonist approach to clear the latent viral reservoir

摘要 目前全球有3400万艾滋病毒携带者，开发一种方式来诱导艾滋病毒功能 治愈是全球健康的重中之重。我们最近发现1)广谱中和抗体能够 2)IL-15超级激动剂ALT-803既能逆转病毒 潜伏并激活体内的自然杀伤细胞。因此，我们假设将ALT-803与广度 CART遮盖下的中和抗体可清除潜伏的蓄水池。为了研究这一有趣的想法，在 R21的特定目标1，我们将建立ALT-803重新激活猕猴潜伏病毒的能力 艾滋病毒的典范。在特定的目标2中，我们将确定ALT-803激活的NK细胞是否能够介导抗体- 依赖细胞介导的对感染细胞的细胞毒作用。如果成功，我们将把ALT-803与Widge结合起来 R33期CART覆盖下的中和抗体。成功完成这些研究可以 定义一种清除潜在储集层的全新方法。

SUMMARY With 34 million people currently living with HIV worldwide, developing a modality to induce an HIV functional cure is a top global health priority. We have recently discovered that 1) broadly neutralizing antibodies are able to potently eliminate the viral reservoir, and 2) that an IL-15 superagonist, ALT-803, is able to both reverse viral latency and activate natural killer cells in vivo. Therefore, we hypothesize that combining ALT-803 with broadly neutralizing antibodies under cover of cART can clear the latent reservoir. To investigate this intriguing idea, in specific aim 1 of the R21, we will establish the ability of ALT-803 to reactivate latent virus in the macaque model of HIV. In specific aim 2, we will determine if ALT-803 activated NK cells can mediate antibody- dependent cell-mediated cytotoxicity on infected cells. If successful, we will combine ALT-803 with broadly neutralizing antibodies under cover of cART in the R33 phase. Successful completion of these studies could define an entirely new approach to clearing the latent reservoir.