Publication date: Dec 08, 2024
A first-in-class vaccine adjuvant delivery system, Mn-ZIF, is developed by incorporating manganese (Mn) into the zinc-containing zeolitic-imidazolate framework-8 (ZIF-8). The mixed metal approach, which allowed for tunable Mn doping, is made possible by including a mild reducing agent in the reaction mixture. This approach allows up to 50% Mn, with the remaining 50% Zn within the ZIF. This multivariate approach exhibits significantly decreased cytotoxicity compared to ZIF-8. The porous structure of Mn-ZIF enables the co-delivery of the STING agonist cyclic di-adenosine monophosphate (CDA) through post-synthetic loading, forming CDA@Mn-ZIF. The composite demonstrated enhanced cellular uptake and synergistic activation of the cGAS-STING pathway, producing proinflammatory cytokines and activating antigen-presenting cells (APCs). In a preclinical Mycobacterium tuberculosis (Mtb) model, CDA@Mn-ZIF formulates with the CysVac2 fusion protein elicited a potent antigen-specific T-cell response and significantly reduced the mycobacterial burden in the lungs of infected mice. These findings highlight the potential of CDA@Mn-ZIF as a promising adjuvant for subunit vaccines, offering a novel approach to enhancing vaccine efficacy and protection against infectious diseases such as tuberculosis.
| Concepts | Keywords |
|---|---|
| Manganese | MOF |
| Metalloimmunological | STING |
| Mycobacterium | tuberculosis |
| Tuberculosis | vaccine |
| Uptake |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | Tuberculosis |
| pathway | KEGG | Tuberculosis |
| disease | MESH | Infection |
| drug | DRUGBANK | Manganese |
| drug | DRUGBANK | Zinc |
| drug | DRUGBANK | Adenosine phosphate |
| disease | IDO | protein |
| disease | IDO | cell |
| disease | MESH | infectious diseases |