Saponin-lipid nanoparticles: From molecular distribution to supramolecular structure

Saponins are a large family of glycoconjugates that share a triterpene structure. When formulated together with phospholipids and cholesterol, they self-assemble into a variety of unique structures depending on the composition. The Matrix-M™ adjuvant consists of two different populations of physically stable nanoparticles based on two different saponin fractions, and has been successfully applied in the clinic in e.g. vaccines against Covid, malaria and veterinary vaccines. Their spherical cage-like structures and structural features have been previously characterised using lab-based methods and SAXS. However, little is understood about the molecular distribution within the saponin-lipid nanoparticles. In this proposal we address this by carrying out a SANS contrast matching study of these particles to elucidate the arrangement of molecules within these cages and to study the overall supramolecular structure label free, at concentrations and temperatures relevant to their application as products in the clinic. The findings from this study present, to our knowledge, the first characterization of the molecular distribution and detailed morphology of these saponin-based nanoparticles. The structural information gathered here will allow a deeper understanding of the interplay between structure and function and are expected to be of high scientific value for the wider community working on saponin and lipid interactions, as well as the vaccine community.