Utilising a systems approach to advance our understanding of immune responses to viral vectors]

病毒载体已成功地用作疫苗和基因治疗。病毒载体疫苗对COVID-19大流行的进程产生了深远影响，仅在2021年，基于病毒载体的疫苗估计就挽救了超过650万人的生命。此外，病毒载体基因疗法大大改善了遗传性疾病患者的生存时间和生活质量。该项目旨在利用当代生物信息学和系统生物学方法来收集对病毒载体的免疫反应的高分辨率视图。对病毒载体的免疫应答是复杂的，并且取决于治疗的目的，所需的免疫应答可能是高度不同的（即，疫苗的免疫刺激相对于基因治疗的免疫逃避）。相反，在病毒载体疫苗和基因疗法的开发中面临着共同的挑战，例如抗载体免疫性、包装能力、转导功效、组织向性、剂量和安全性。为了优化病毒载体的使用，需要更好地了解它们与免疫系统的相互作用。最近在基因组学、表观基因组学、转录组学和蛋白质组学领域的技术进步，提供了以前所未有的分辨率揭示病毒载体免疫应答的机会。这些数据可能会彻底改变基于病毒载体的疗法的使用方式

Viral vectors have been used successfully as vaccines and gene-therapies. Viral vector vaccines had a profound impact on the course of the COVID-19 pandemic, with estimates of over 6.5 million lives saved in 2021 alone due to viral vector-based vaccines. Moreover, viral vector gene therapies have drastically improved both the duration and quality of life of patients with hereditary diseases. This project aims to utilise contemporary bioinformatic and system biology approaches to glean a high-resolution view of immune responses to viral vectors. The immune response to viral vectors is complex and depending on the purpose of therapy the desired immune responses may be highly disparate (i.e., immunostimulatory for vaccines versus immune evasion for gene therapy). Conversely, common challenges are faced in the development of both viral vector vaccines and gene therapies such as anti-vector immunity, packaging capabilities, transduction efficacy, tissue tropism, dosing, and safety. To optimise the use of viral vectors, a better understanding of their interaction with the immune systems is required. Recent technological advances, in the areas of genomics, epigenomics, transcriptomics and proteomics, offer the opportunity to reveal the immunology underlying responses to viral vectors at an unprecedented resolution. These data could revolutionize the way viral vector-based therapies are used