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

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