Astragalus polysaccharides combined with simvastatin as an immunostimulant enhances the immune adjuvanticity of oil-in-water emulsion and immune responses in mice

Oil-in-water emulsion-based adjuvants have demonstrated acceptable safety in many disease indica-tions, while their adjuvant activities for vaccines still need to be improved. Recently, the strategy of com-bining adjuvants with multiple types of immunostimulants has been shown to enhance immune responses. In this study, astragalus polysaccharides were combined with simvastatin as an immunostim-ulant to construct a compound O/W emulsion adjuvant. The formulations were optimized according to the OVA-specific antibody responses induced in mice. For this reason, high (5 mg/mL), medium (2.5 mg/mL), and low (1.25 mg/mL) concentrations of astragalus polysaccharides and high (10 mg/mL), medium (1 mg/mL), and low (0.1 mg/mL) concentrations of simvastatin were selected. The final optimal formulation of the immunostimulant was a high concentration of astragalus polysaccharides combined with a medium concentration of simvastatin. The optimal compound O/W emulsion adjuvant could induce effective humoral and cellular immune responses that were stronger and more stable than those induced by aluminum adjuvant and Freund's adjuvant. The OVA/HAPS-MSim-OE induced dramatically strong and persistent IgG expressions and Th1-polarized immune responses. What's more, the highest CD4+/CD8+lymphocyte ratios were observed in OVA/HAPS-MSim-OE group. In addition, compound O/ W emulsion adjuvant groups significantly promoted the secretion of IFN-c and IL-6, which also indicated that the compound O/W emulsion adjuvants could induce both enhanced Th1 and Th2-mediated immune responses but prefer the Th1-mediated ones. This study would contribute to an interesting and promising direction in the development of emulsion-based adjuvants. (c) 2023 Elsevier Ltd. All rights reserved.