Rational Design of T cell vaccines

Dr Leo Swadling; Division of Infection and Immunity, UCL

I am a group leader in the Infection and Immunity division at UCL, supported by a Wellcome Trust Career Development Award, UKRIDPFS, and Rosetrees Trust funding. I did my PhD at the University of Oxford, developing genetic and molecular technologies to optimise T cell vaccines for hepatitis C with Profs Ellie Barnes & Paul Klenerman. I moved to London to study tissue-residency and liver immunology with Prof Mala Maini and to characterise T cell responses to SARS-CoV-2 as part of UK-CIC (www.uk-cic.org/),COVIDsortium (covid-consortium.com/) and IMMPROVE (immprove.ac.uk/) consortia. I established the T cell vaccine lab at UCL in2022.

In the T cell vaccine group we study the ability of the immune system to cross-recognise viruses that exist as a swarm of closely related but variant sequences geographically, over time, and even within a single host. We aim to establish T-cell correlates of protection by integrating high-resolution single-cell studies of T-cell quality (function, phenotype, trafficking) and specificity (virus, protein, epitope, TCR clonality) in natural history studies, studying the extremes of controlled (e.g. abortive infection) and uncontrolled viral replication (severe acute and chronic infection). Ultimately, we will rationally design vaccines to recapitulate these correlates to see if this will lead to better vaccines. We investigate cross-reactivity, immunodominance, antigen processing and presentation, and utilise in silico ML tools and large scale viral sequence analysis to inform vaccine design.