Metal-Organic Framework Encapsulated Whole-Cell Vaccines Enhance Humoral Immunity against Bacterial Infection

Abstract

Urinary tract infection, most often caused by uropathogenic Escherichia coli (UPEC), is the second most common bacterial infection. Rates of antibiotic resistance among UPEC strains is high and front-line antibiotic therapies are losing efficacy. Untreated, UPEC can ascend to the kidneys and into the bloodstream to cause potentially fatal pyelonephritis and bacteremia, respectively. Vaccine development is hampered by the genetic diversity of UPEC strains making selection of antigens capable of inducing broad protection difficult. Whole cell UPEC vaccines offer a solution to the antigen selection problem, however, current inactivation methods are harsh and degrade surface antigens resulting in a weak immune response. Here, we demonstrate a method to gently inactivate whole cell UPEC by encasing them in a crystalline metalcoordination polymeric matrix called a Metal-Organic Framework. This process encapsulates read-to-use composites within 30 minutes in water and at ambient temperatures. We show this new formulation greatly improves survivability in a murine model of UPEC bacteremia compared to standard inactivated formulations. The simplicity of the preparation and use suggests this method could be applied as a point-of-care measure to create therapeutic and prophylactic vaccines against patient derived samples.

Stabilization of Supramolecular Membrane Protein-Lipid Bilayer Assemblies Through Immobilization in a Crystalline Exoskeleton

“…[27][28][29] ZIF-8 in particular is well known for its ability to nucleate on the surface of colloidal and dissolved biomacromolecules forming a crystalline matrix shell. 30,31 We suspected that colloidal liposomes, proteoliposomes, and detergent solubilized transmembrane proteins would nucleate the growth of ZIFs over their surface, and this protective shell would inhibit both protein denaturation and liposome fusion and/or degradation. Further, the kinetic lability of Zn-MIM bond in the presence of high-affinity metal chelators would allow us to recover the encapsulated systems without significant loss of protein function or sample homogeneity.…”

Biomimetic Assembly of Spore@ZIF‐8 Microspheres for Vaccination

“…Moreover, the IgG titer induced by the OZ was 5 times that of free OVA, indicating that protective depot formed via ZIF‐8 may enhance the humoral immune response by controlling the release of antigen protein. [ 35 ] Importantly, the IgG titer induced by the SOZ was significantly higher than that of the spore mixture, which might be caused by the protective antigen depot formed via ZIF‐8 on the SOZ surface. Additionally, the antibody level of the SOZ‐1M group was the same with that of the SOZ group (Figure 3a), demonstrating the antibody inducing activity of the protein cargo in SOZ was stable for at least one month after storage at 4 °C.…”

Enhancing the Stability of COVID‐19 Serological Assay through Metal–Organic Framework Encapsulation

“…Metal-organic frameworks (MOFs), comprised of polynuclear metal clusters or ions bridged by organic ligands, have increasingly received wide interests. [19][20][21][22][23] MOFs exhibit extremely large surface area, tunable porosity, diverse chemical functionality, and high thermal stability, [21][22][23] making them highly attractive for biomineralization, [24] encapsulation, [25] biosensors, [26] drug delivery, [27] gas storage, [28] and catalysis. [29] Among these applications, of particular interest is the encapsulation of biomolecules via in situ growth of MOF crystals in the presence of biomolecules at room temperature under mild aqueous conditions.…”

“…[29] Among these applications, of particular interest is the encapsulation of biomolecules via in situ growth of MOF crystals in the presence of biomolecules at room temperature under mild aqueous conditions. [24][25][26][30][31][32][33] MOFs serve as rigid exoskeletons, preserving the structure and biofunctionality of embedded molecules against denaturation/degradation under elevated temperature, organic solvents, and proteolytic conditions. [24,26] Although MOF encapsulation has been demonstrated for preserving enzymes, soluble proteins/biomarkers and antibodies in biosensors, preserving immobilized antigens in an immunoassay has not been demonstrated.…”