Vaccines represent one of the most potent strategies for protecting humans from the threat of infectious diseases. Conventional vaccines elicit acquired immunity by mimicking pathogen characteristics; however, their protective efficacy is limited by inadequate spatiotemporal control of antigen delivery, resulting in suboptimal antigen exposure in lymphoid tissues and transient adaptive immune activation. Here, we developed a self-assembling peptide-based supramolecular hydrogel vaccine to establish a localized immune niche, demonstrating its remarkable efficacy in inducing durable and potent immunity against infectious diseases. We found that this in situ-formed supramolecular hydrogel vaccine serves as a reservoir for antigens and adjuvants while recruiting antigen-presenting dendritic cells (DCs) to accumulate within the scaffold. With the aid of adjuvant, the DCs exhibit enhanced antigen processing and presentation, creating an immunologically active niche that triggers robust B cell and T cell responses. Following a single vaccination, mice immunized with the hydrogel vaccine developed robust humoral immunity and sustained antibody production for 112 days, achieving potent neutralization activity. This study offers a novel approach to spatiotemporal control of vaccine responses that enables durable and enhanced immunity against infectious diseases.

Self-assembling peptide  /  Supramolecular nanofiber  /  Hydrogel scaffold  /  Immune niche  /  Vaccine  /  Infectious disease  /  Single vaccination  /  Durable immunity