Linking physio-chemical properties of adjuvants to immunological responses for the rational design of next generation vaccines

Lead supervisor:  Prof. Anita Milicic 

Co-supervisor: Prof. Dermot O'Hare

Commercial partner: iuvantium

Developing new potent, safe and durable vaccine modalities is imperative in the face of pathogen outbreaks and future pandemics. Vaccine adjuvants are a potent platform that can satisfy this need. However, the best adjuvant compounds are proprietary, inaccessible to academic vaccine developers and to the wider research community. Moreover, due to our inadequate understanding of their mechanism of action, current adjuvants cannot be rationally tailored to fit different disease settings, presenting a major hindrance to designing formulations for successful clinical deployment. In particular, innate immune responses to vaccines are poorly described and largely neglected by vaccinologists. Yet these early events dictate the quality, strength and kinetics of the subsequent adaptive immunity, and ability to provide durable protection.

For this iCASE studentship we partner with iuvantium, an Oxford-based start-up that is rationally designing and engineering novel inorganic compounds as vaccine adjuvants, in a cross-disciplinary approach to next generation vaccine design. The chemical composition of these compounds directly controls their immunological properties (Williams et al., JEM, 2014), with specific types of immune responses induced by tailoring physico-chemical properties, e.g. particle size and surface chemistry.

Using established in vitro and in vivo pre-clinical models, with SARS-CoV-2 Spike protein as antigen, the project will characterise in detail the innate and adaptive immune responses to an available library of inorganic modulators to establish parameters for further mechanistically informed adjuvant design. Adjuvant-induced signalling will be assessed in a range of innate immune cell types, and aligned with the ensuing adaptive responses in mice. Machine learning will be employed to iteratively improve adjuvant chemistry and morphology for improved performance. Vaccine efficacy will be determined using pseudo-virus neutralisation assays, to identify the most promising compounds for further clinical development.

This cross-disciplinary project offers the candidate the unique opportunity to get trained across a range of disciplines, from inorganic chemistry to cellular and systemic immunology, and the prospect to experience creative research at an immunobiology start-up in addition to the mechanistically informed approach to rational vaccine design at the Jenner Institute.

Apply using course: DPhil in Clinical Medicine