美国约翰霍普金斯大学Robert F. Siliciano等研究人员合作发现，双特异性抗体促进自然杀伤细胞介导的HIV-1储存细胞的清除。2024年1月26日，《自然—免疫学》杂志在线发表了这项成果。

研究人员报告了两种针对人类免疫缺陷病毒-1（HIV-1）包膜蛋白（Env）和人类III型Fcγ受体（CD16）的单链二抗体（scDbs）。研究表明，scDbs能促进稳健的、HIV-1特异性自然杀伤（NK）细胞活化和NK细胞介导的感染细胞裂解。将接受抗逆转录病毒疗法（ART）的HIV-1感染者的CD4⁺ T细胞与自体NK细胞和scDbs共培养，可明显消除储库细胞，而这取决于潜伏期的逆转。

在开始接受抗逆转录病毒疗法后，用其中一种scDbs治疗人类白细胞介素-15转基因NSG小鼠，可增强NK细胞的活性并减少储库细胞的数量。因此，HIV-1特异性scDbs作为清除潜伏库的潜在疗法值得进一步评估。

据介绍，携带潜伏HIV-1前病毒的CD4⁺ T细胞的持续存在是治愈的主要障碍。要减少潜伏病毒库，可能需要新的疗法来增强HIV-1特异性免疫反应和清除受感染的细胞。

附：英文原文

Title: Bispecific antibodies promote natural killer cell-mediated elimination of HIV-1 reservoir cells

Author: Board, Nathan L., Yuan, Zhe, Wu, Fengting, Moskovljevic, Milica, Ravi, Meghana, Sengupta, Srona, Mun, Sung Soo, Simonetti, Francesco R., Lai, Jun, Tebas, Pablo, Lynn, Kenneth, Hoh, Rebecca, Deeks, Steven G., Siliciano, Janet D., Montaner, Luis J., Siliciano, Robert F.

Issue&Volume: 2024-01-26

Abstract: The persistence of CD4+ T cells carrying latent human immunodeficiency virus-1 (HIV-1) proviruses is the main barrier to a cure. New therapeutics to enhance HIV-1-specific immune responses and clear infected cells will probably be necessary to achieve reduction of the latent reservoir. In the present study, we report two single-chain diabodies (scDbs) that target the HIV-1 envelope protein (Env) and the human type III Fcγ receptor (CD16). We show that the scDbs promoted robust and HIV-1-specific natural killer (NK) cell activation and NK cell-mediated lysis of infected cells. Cocultures of CD4+ T cells from people with HIV-1 on antiretroviral therapy (ART) with autologous NK cells and the scDbs resulted in marked elimination of reservoir cells that was dependent on latency reversal. Treatment of human interleukin-15 transgenic NSG mice with one of the scDbs after ART initiation enhanced NK cell activity and reduced reservoir size. Thus, HIV-1-specific scDbs merit further evaluation as potential therapeutics for clearance of the latent reservoir.

DOI: 10.1038/s41590-023-01741-5

Source: https://www.nature.com/articles/s41590-023-01741-5