'Designer' Inorganic Vaccine Adjuvants

Effective vaccines need to contain both an antigen, e.g. a viral, microbial or tumour component, and crucially an adjuvant. The role of a vaccine adjuvant is to reproduce or mimic the ‘danger signals‘ that naturally trigger immune responses and so enhance the efficiently of the vaccine. Very few vaccine adjuvants are currently licensed for human use, they are poorly understood mixtures of aluminium and magnesium salts, and it appears that even the most basic understanding of the chemistry of these materials is almost totally lacking. This research grant application proposes to study carefully prepared pure inorganic compounds with well defined composition, size and shape so that we can begin to unravel the chemical and structure factors that affect the efficient of vaccine adjuvants. If successful, this project will offer the exciting possibility of creating the next generation of effective, safe and cheap inorganic adjuvants for global use in vaccination.

The purpose of this Discipline Hopping application is to support research that plans to take synthetic Inorganic Chemistry into Immunology. Inorganic aluminium compounds such as alum(s) are currently used to enhance immunity induced by vaccines. Remarkably, it appears that even the most basic understanding of the inorganic chemistry of the alum(s) used as vaccine adjuvants is almost totally lacking. We propose to prepare a series of tailor-made metal hydroxides known as Layered Double Hydroxides (LDHs) with specific chemical composition, crystal size and morphology that are designed to unravel the physico-chemical factors that control the vaccine adjuvanticity of inorganic metal hydroxides. Through the collaboration with the Department of Surgery we propose to learn how to evaluate the immunological properties of these LDHs. We propose to develop a relatively simple but informative assay in order to identify lead compounds that can subsequently be assessed for their adjuvant properties in vivo. For example, an important function of adjuvants is to induce the secretion of pro-inflammatory cytokines such as IL-1 by cells such as dendritic cells and macrophages. We proposed to learn both culture techniques for growing these cell types and the analytics for detecting the key signalling molecules.