Quillaja saponaria fraction QS-18 as an adjuvant for liposomal seasonal influenza vaccines

Saponin fractions from Quillaja saponaria (QS) are promising vaccine adjuvants. Among these, QS-21 is a component in several FDA-approved vaccines, but its limited quantity may present a manufacturing bottleneck. While the related saponin, QS-18, is one of the most abundant fractions, its putative toxicity has historically hindered its clinical development. In this study, we formulated QS-18 into a seasonal influenza virus liposomal nanoparticle protein vaccine comprising contemporary, recombinant hemagglutinin and neuraminidase antigens from influenza A (H1N1), influenza A (H3N2), and influenza B (Victoria lineage). This formulation did not exhibit overt QS-18 toxicity in mice or rabbits. In mice and ferrets, QS-18 adjuvanted particles elicited efficacious antibody responses and provided protection against influenza challenges, comparable to analogous QS-21 adjuvanted liposomes. These findings suggest that more study of QS-18 or QS-18-containing QS fractions is warranted for infectious disease vaccine adjuvant formulations.