Self-assembled Ac-FFA-NH2 based hydrogels with strong immunostimulating activity for vaccine delivery

Abstract

Recent research has demonstrated that peptide self-assemblies are effective as vaccine adjuvants, playing a critical role in enhancing vaccine efficacy. In our prior studies, the Ac-FFA-NH₂ peptide gelator was identified as a biocompatible material suitable for tissue engineering applications. In this study, we reveal that the self-assembled Ac-FFA-NH₂ hydrogel functions as a potent vaccine delivery system, as evidenced by its strong immunostimulatory activity in vivo. Mice vaccinated with OVA antigen incorporated into the hydrogel produced significantly higher IgG titers compared to both the unadjuvanted control group and those treated with traditional adjuvants. This suggests that the Ac-FFA-NH₂ hydrogel effectively induces a robust humoral immune response. Moreover, the hydrogel not only enhances humoral immunity but also stimulates a cellular immune response, as indicated by the production of the IgG2a subtype, further establishing it as an excellent vaccine delivery platform. Additionally, we describe a composite hydrogel developed through the stepwise self-assembly of the Ac-FFA-NH₂ peptide and liposomes. Structural characterization using TEM, DSC, and FTIR confirmed that both peptide nanofibers and lipid vesicles retain their structural integrity within the composite gel. Importantly, morphological analysis demonstrated that the mechanical robustness of the hydrogel remains largely unaffected by the presence of liposomes at lipid concentrations lower than the Ac-FFA-NH₂ concentration.