Yeast-Derived Manganese and Zinc Metal–Organic Framework Composite as a Vaccine Adjuvant for Enhanced Humoral and Cellular Immune Responses

To control pandemics, a universal adjuvant platform that can deliver antigens and stimulate the immune system that rapidly elicits humoral and cellular immune responses is needed, especially one that can stimulate the body's immune system to produce protective immunological memory. However, the design, composition, and mechanism of adjuvants have presented considerable challenges. The types of adjuvants currently approved in clinics are rare and are far from meeting the requirements of vaccine development. In this study, we prepared a yeast-derived manganese and zinc metal-organic framework (MOF) composite particle adjuvant by self-assembling Mn-MOF-74 and ZIF-8 on the surface of yeast and named it yeast@Mn-MOF-74@ZIF-8 (yMZ). yMZ was able to promote the maturation and activation of dendritic cells (DCs), enhance the uptake and presentation of antigens by DCs, increase the production of adaptive immune cells with memory, enhance humoral and cellular immune responses, and promote the activation of the germinal center. Additionally, yMZ allowed for effective control of antigen release and exhibited good biosafety in vivo. In this study, yMZ showed good adjuvant effects on subunits and inactivated vaccines, indicating that it is a next-generation adjuvant candidate with potential application prospects.