A Minimalist Pathogen‐Like Sugar Nanovaccine for Enhanced Cancer Immunotherapy

Pathogen-mimicking nanoparticles have emerged at the forefront of vaccine delivery technology, offering potent immune activation and excellent biocompatibility. Among these innovative carriers, mannan, a critical component of yeast cell walls, shows promise as an exemplary vaccine carrier. Nevertheless, it faces challenges like unpredictable immunogenicity, rapid elimination, and limited antigen loading due to high water solubility. Herein, mannan with varying carbon chain ratios is innovatively modified, yielding a series of dodecyl chains modified mannan (Mann-C₁₂). Through meticulous screening, a mannan variant with a 40% grafting ratio is pinpointed as the optimal vaccine carrier. Further RNA sequencing confirms that Mann-C₁₂ exhibits desired immunostimulatory characteristics. Coupled with antigen peptides, Mann-C₁₂/OVA_257-280 nanovaccine initiates the maturation of antigen-presenting cells by activating the TLR4 and Dectin-2 pathways, significantly boosting antigen utilization and sparking antigen-specific immune responses. In vivo, experiments utilizing the B16-OVA tumor model underscore the exceptional preventive capabilities of Mann-C₁₂/OVA_257-280. Notably, when combined with immune checkpoint blockade therapy, it displays a profound synergistic effect, leading to marked inhibition of tumor growth. Thus, the work has yielded a pathogen-like nanovaccine that is both simple to prepare and highly effective, underscoring the vast potential of mannan-modified nanovaccines in the realm of cancer immunotherapy.