Vaccine Formulation and Adjuvants
We study the immune mechanisms of action of vaccines and vaccine adjuvants, taking an integrated approach in combining murine models with ex vivo human lymphoid tissue and clinical studies. We are also working on developing single-dose vaccine formulations: the aim is to deliver prime-bost vaccination with a single administration, where the booster vaccine is encapsulated for a delayed burst-release in vivo.
The focus of our group are studies of immune mechanisms underlying vaccine immunogenicity and efficacy, with a specific emphasis on vaccine adjuvants. Adjuvants include a diverse range of compounds that have the ability to potentiate vaccine efficacy.
We are exploring the mechanism of action of vaccines delivered using different vaccine platforms, including viral vectors, and virus like particles (VLPs) and proteins formulated with novel adjuvants developed by the Vaccine Formulation Institute (VFI) in Geneva and supported by the Gates Foundation. In late 2019 we initiated the VFI-Oxford Adjuvant Programme of research with three primary goals: i) understand the type, magnitude and kinetics of responses induced by different clinically-compatible adjuvants, ii) characterise the adjuvant immunogenicity profiles with different clinically relevant antigens and iii) assess vaccine efficacy through challenge studies in pre-clinical models of disease. These questions are being addressed through spatio-temporal studies of the innate and adaptive immune responses to adjuvanted vaccines, using established mouse models of disease, high resolution transcriptomic approaches and in vitro cellular model systems.
To complement the animal model studies, and with the support from the Chan Zuckerberg Initiative, we are studying the initial events in adjuvant-induced inflammation in humans. Using ex vivo human lymph nodes, in combination with single cell RNA sequencing and hyperplexed imaging, we are working to create a high-resolution transcriptomic and proteomic map of the early innate immune responses to vaccine adjuvants. This work synergises with a clinical study detailing the lymph node and systemic immune response to vaccines in individuals of different ethnicities, carried out in partnership with the Imperial College London as part of the LEGACY Network.
Our third programme of research is on single-dose vaccines. In collaboration with the Institute for Biomedical Engineering (IBME), we are developing new microfluidics-based vaccine encapsulation technologies for controlled vaccine release. The aim is to achieve single-dose immunisation that could replace the standard prime-boost approach: the booster vaccine is encapsulated into microcapsules and delivered together with the prime, for a delayed burst release within the body.