Lipid-coated biodegradable particles as “synthetic pathogens” for vaccine engineering

The physicochemical context in which molecules are presented at the surfaces of microbes has tremendous implications for the immune response to vaccination. The spacing and mobility of molecules may control interactions of their receptors, influencing immune cell activation, pathogen uptake, and antigen processing. The chemical environment of antigens also influences the specificity of the humoral immune response, because antibodies recognize antigen in its three-dimensional shape and context. Finally, physical properties of antigen, such as diameter, impact immune response on both a cellular and tissue level. We have constructed ldquosynthetic pathogensrdquo consisting of a biodegradable core polymer coated by a lipid shell to mimic a bilayer-enveloped pathogen. Synthesized in an oil-in-water emulsion, these particles have an average diameter on the order of either 100 nm, mimicking a lipid-enveloped viral pathogen, or 1 micron, mimicking a bacterial pathogen. CryoEM reveals self-assembled lipid layers at the particle surface. With tunable chemical and physical properties, these particles can be used to study the importance of specific properties of biomaterials when used in vaccination. Because all components are biodegradable, the particles may provide a clinically applicable way of implementing structural features of microbes in synthetic vaccines.