Exploiting Natural Killer cells in HIV/HBV co-infection to achieve eradication

在HIV/HBV合并感染中利用适应性NK细胞实现根除 项目总结/摘要 尽管联合抗逆转录病毒治疗（ART）具有双重抗艾滋病毒活性， 和HBV，HIV/HBV合并感染与HBV单一感染之间的结果差异 人口仍然存在。我们目前对免疫恢复程度的理解 在这两组中，特别是在肝脏免疫应答方面的治疗是罕见的， 确定一个重大的知识差距和障碍，以发展有效的功能， 治愈最近的技术进步，包括使用单细胞RNA测序（scRNA- seq）和高通量单细胞分析沿着，以及细针抽吸物（FNA）。 来自适当匹配的临床队列的肝脏提供了新的令人兴奋的机会来探索 肝脏与外周免疫特征。这些创新方法将应用于 确定免疫细胞的转录景观，蛋白质组学和功能特征 HIV/HBV合并感染与HBV单一感染之间的肝脏和外周血中的人群 感染的病人在一个全新的分辨率水平。将特别强调 具有适应性的自然杀伤（NK）细胞和具有适应性的独特NK细胞亚群 “记忆”功能在肝脏中富集。这些出现在 对慢性病毒感染和接种HIV编码包膜疫苗后的反应 蛋白质和赋予增强的功能性具有巨大的潜力， 控制病毒复制。因此，适应性NK细胞的临床开发代表了一种新的方法。 这是一种增强慢性病毒感染治疗的变革性方法。我们的目标是发展一个 用于扩增适应性NK细胞的强大且可扩展的平台， 功能和可预测的选择性，可以规避许多固有的限制， 到目前为止测试的各种免疫方法，代表了一种新的途径， 新的或补充的治疗策略。

Exploiting adaptive NK cells in HIV/HBV co-infection towards eradication Project Summary/Abstract Despite the benefits of combined antiretroviral treatment (ART) with dual activity against HIV and HBV, the differences in outcome between HIV/HBV co-infected and HBV mono-infected populations still persist. Our current understanding of the degree of immunological recovery with therapy in these two groups, in particular in terms of hepatic immune responses is scarce, identifying a significant knowledge gap and a barrier to the development of effective functional cures. Recent technical advances, including the use of single-cell RNA sequencing (scRNA- seq) and high-throughput single cell analysis along with fine needle aspirates (FNAs) of the liver from appropriately matched clinical cohorts provide new exciting opportunities to probe hepatic versus peripheral immune signatures. These innovative approaches will be applied to ascertain the transcriptional landscape, proteomic and functional features of immune cell populations in the liver and peripheral blood between HIV/HBV co-infected versus HBV mono- infected patients at an entirely new level of resolution. Particular emphasis will be placed on Natural Killer (NK) cells with adaptive properties and unique subpopulations of NK cells with ‘memory’ features enriched in the liver. These specialised subpopulations that arise in response to chronic viral infections and following vaccination with HIV-encoded envelope protein and endowed with enhanced functionality hold tremendous potential for effective control of virus replication. Therefore, clinical exploitation of adaptive NK cells represents a transformative approach to augment therapy of chronic viral infection. We aim to develop a robust and scalable platform for the expansion of adaptive NK cells with enhanced functionality and predictable selectivity that could circumvent many of the limitations inherent to the various immunotherapeutic approaches tested so far, representing a novel avenue for new or complementary curative strategies.