MF59-like adjuvant containing yeast-derived squalene enhances the humoral immune response to cell-derived influenza vaccine

The aims of this study were to assess the adjuvant properties of an MF59-like adjuvant containing yeast-derived squalene (MF59-like YD) in a cell-based quadrivalent influenza vaccine (QIV) and to investigate the potential mechanisms of action. MF59-like adjuvants containing either yeast-derived or shark-derived squalene were incorporated into QIV formulations. Antigen-specific immune responses in mouse serum were evaluated via enzyme-linked immunosorbent assays (ELISAs), hemagglutination inhibition (HI) assays, and microneutralization (MN) assays. The effects and mechanisms of action of the adjuvants were further analyzed by analyzing mouse spleen germinal center (GC) cell activation via flow cytometry. MF59-like YD significantly increased the humoral immune responses induced by QIVs in mice, in particular, the titers of HI and MN antibodies against homologous and heterologous virus subtypes. Mechanistically, MF59-like YD increased the immune response to influenza vaccines by activating T follicular helper (Tfh) and B cells in the GC. Given the greater availability of yeast-derived squalene and the finding that its adjuvant efficacy was comparable to that of shark-derived squalene, we propose that the MF59-like YD adjuvant is a promising alternative adjuvant for future influenza vaccines.