There is currently no paradigm in immunology that enables accurate prediction of how the immune system will respond to any given agent. Here we show that the immunological responses induced by members of a broad class of inorganic crystalline materials are controlled purely by their physicochemical properties, in a highly predictable manner. We show that structurally and chemically homogeneous layered double hydroxides (LDHs) can elicit diverse human dendritic cell (DC) responses in vitro. Using a systems vaccinology approach we find that every measured response can be modelled using a subset of just three physical and chemical properties, for all compounds tested. This correlation can be reduced to a simple linear equation which enables the immunological responses stimulated by newly-synthesised LDHs to be predicted in advance, from these three parameters alone. We also show that mouse antigen-specific antibody responses in vivo, and human macrophage responses in vitro, are controlled by the same properties, suggesting they may control diverse responses at both individual component, and global, levels of immunity. This study demonstrates that immunity can be determined purely by chemistry, and opens the possibility of rational manipulation of immunity for therapeutic purposes.
The Journal of Experimental Medicine