A Mn²⁺-Assisted Nanofiber-Hydrogel Adjuvant for Simultaneous Enhancement of Humoral and Cellular Immune Responses

Limited ability to elicit cellular immune responses has restricted the effectiveness of conventional adjuvants in the context of cancers. Recent advancements in innate immune activation mechanism investigations have paved the way for the implementation of a "bottom-up" approach in the development of novel adjuvants. Herein, a simple hydrogel adjuvant with a uniformly organized nanoscale microstructure, termed MnPgel is devised, by employing self-assembling peptides incorporated with manganese ions (Mn2+). MnPgel exhibits Mn2+ sustained-release properties in vivo and effectively promotes germinal center formation, thereby facilitating the generation of antibodies at levels comparable to conventional aluminum-based adjuvants. Moreover, MnPgel transcends the scope of humoral immunity, demonstrating the ability to robustly trigger cellular immune responses and positioning it as a promising candidate for cancer prevention and treatments. In conclusion, the work has introduced a well-defined hydrogel adjuvant as a proof-of-concept, simplifying vaccine adjuvant design and opening up new avenues for "on-demand" immunomodulation strategies.