Affiliation:
1. Institute of Functional Nano & Soft Materials (FUNSOM) Jiangsu Key Laboratory for Carbon‐Based Functional Materials & Devices Soochow University Suzhou 215123 China
2. School of Materials Science and Engineering Tongji University Shanghai 201804 China
3. Department of Thoracic Surgery Shanghai Pulmonary Hospital School of Medicine Tongji University Shanghai 200433 China
4. Central Laboratory Shanghai Pulmonary Hospital School of Medicine Tongji University Shanghai 200433 China
Abstract
AbstractPathogen‐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/OVA257‐280 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/OVA257‐280. 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.
Funder
National Natural Science Foundation of China
Program of Shanghai Academic Research Leader