Controlled Lipid Self-Assembly for Scalable Manufacturing of Next-Generation Immune Stimulating Complexes

Methods of controlled lipid self-assembly for scalable manufacturing of next-generation immune stimulating complexes (ISCOMs) are described. The methods involve mixing one or more saponins, one or more lipids, one or more sterols, one or more additional adjuvants (e.g., TLR4 agonist), and optionally one or more antigens in the presence of a detergent. Typically, the mixing step is followed by an incubation step, a dilution and/or concentration step, and/or a filtration or dialysis step for removing detergent. Preferably, methods involve a tangential flow filtration (TFF) process suitable for scalable synthesis and Good Manufacturing Practice (GMP) production of highly homogeneous clinical-grade ISCOM-based adjuvants.