A research team from the Chinese Academy of Sciences has developed a groundbreaking approach to vaccine design by enhancing immune activation through deformable adjuvants. Led by Prof. Xia Yufei from the Institute of Process Engineering (IPE), this study highlights a novel method to improve immune responses, particularly in elderly and immunocompromised populations. The findings were published on January 8, 2026, in the journal Cell Biomaterials.
Conventional vaccine adjuvants primarily focus on biochemical stimulation and molecular binding to enhance immune responses. However, these traditional methods often yield limited efficacy, particularly among older adults or individuals with weakened immune systems. The challenge has been to incorporate physical regulation into immune activation effectively.
The research team tackled this issue by redesigning aluminum adjuvants into a deformable, three-dimensional mechanical interface. They constructed aluminum-stabilized Pickering emulsions (ASPEs) that allow dendritic cells (DCs) to actively sense mechanical cues at the interface. This innovative approach significantly amplifies immune responses compared to conventional particulate adjuvants.
The ASPE droplets exhibit deformation upon contact with DC membranes, which increases the interfacial contact area and enables the delivery of controllable mechanical stress. By adjusting the crystallinity of aluminum nanoparticles, the researchers can precisely regulate the interfacial stiffness, allowing for graded mechanical stimulation.
Stronger mechanical cues directly activate the mechanosensitive ion channel PIEZO1, leading to an influx of calcium ions (Ca2+), which promotes antigen cross-presentation. When combined with the TLR4 agonist monophosphoryl lipid A (MPLA), the ASPE platform achieves a synergistic mechano-biochemical activation. This results in improved dendritic cell maturation, enhanced Th1-biased immunity, and robust CD8+ T-cell responses.
The effectiveness of this new formulation, known as ASPE-M, demonstrates marked advantages over the clinically used Alum+MPLA combination. The study showed that ASPE-M induces stronger immune responses, particularly in aged mouse models. These findings suggest significant potential for improving therapeutic outcomes in dendritic cell-based melanoma immunotherapy, especially when used alongside PD-1 blockade.
Overall, this research establishes the importance of interfacial mechanics as a programmable dimension of immune regulation. It complements traditional biochemical signaling, offering a promising strategy for vaccine and immunotherapy design. The implications of this work could lead to substantial improvements in immune efficacy among aging and immunocompromised populations, marking a significant advancement in the field of immunology.
For further details, see the study by Yali Ming et al., titled “Drilling dendritic cell activation: Engineering interfacial mechano-biochemical cues for enhanced immunotherapy,” published in Cell Biomaterials (2025). DOI: 10.1016/j.celbio.2025.100281.
