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

总结 目前全世界有3400万人感染艾滋病毒，开发一种诱导艾滋病毒功能的方法， 治愈是全球卫生的首要任务。我们最近发现，1）广泛中和抗体能够 有效地消除病毒储库，和2）IL-15超激动剂ALT-803能够逆转病毒储库， 潜伏和激活体内自然杀伤细胞。因此，我们假设ALT-803与广泛的 cART覆盖下的中和抗体可以清除潜在的水库。为了研究这个有趣的想法，在 R21的特定目的1，我们将确定ALT-803在猕猴中重新激活潜伏病毒的能力 艾滋病模型。在具体目标2中，我们将确定ALT-803激活的NK细胞是否可以介导抗体-NK细胞。 依赖于细胞介导的对感染细胞的细胞毒性。如果成功，我们将联合收割机ALT-803与广泛的 在R33阶段，在cART的掩护下中和抗体。成功完成这些研究可以 定义了一种全新的方法来清除潜在的水库。

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.