Metal–Organic Coordination Polymer for Delivery of a Subunit Broadly Acting Influenza Vaccine

Abstract

A zinc-carnosine (ZnCar) metal−organic coordination polymer was fabricated in biologically relevant N-(2hydroxyethyl)piperazine-N′-ethanesulfonic acid (HEPES) buffer for use as a vaccine platform. In vitro, ZnCar exhibited significantly less cytotoxicity than a well-established zeolitic imidazolate framework (ZIF-8). Adsorption of CpG on the ZnCar surface resulted in enhanced innate immune activation compared to soluble CpG. The model antigen ovalbumin (OVA) was encapsulated in ZnCar and exhibited acid-sensitive release in vitro. When injected intramuscularly on days 0 and 21 in C57BL/6 mice, OVA-specific serum total IgG and IgG1 were significantly greater in all groups with ZnCar and antigen compared to soluble controls. Th1-skewed IgG2c antibodies were significantly greater in OVA and CpG groups delivered with ZnCar for all time points, regardless of whether the antigen and adjuvant were co-formulated in one material or co-delivered in separate materials. When broadly acting Computationally Optimized Broadly Reactive Antigen (COBRA) P1 influenza hemagglutinin (HA) was ligated to ZnCar via its His-tag, significantly greater antibody levels were observed at all time points compared to soluble antigen and CpG. ZnCar-formulated antigen elicited increased peptide presentation to B3Z T cells in vitro and production of IL-2 after ex vivo antigen recall of splenocytes isolated from vaccinated mice. Overall, this work displays the formation of a zinc-carnosine metal−organic coordination polymer that can be applied as a platform for recombinant protein-based vaccines.

Metal–organic coordination polymers for delivery of immunomodulatory agents, and infectious disease and cancer vaccines

“…The patterns obtained by PXRD can only be elucidated when compared to a diffractogram previously reported in literature, or as a simulated model. For example, Eckshtain‐Levi et al reported a zinc‐carnosine CP and confirmed the structure via predicted simulations of PXRD patterns (Eckshtain‐Levi et al, 2022).…”

“…Eckshtain‐Levi et al reports a zinc‐based CP where the organic linker is carnosine, a dipeptide that is already found in the body in high amounts in muscle tissue (Eckshtain‐Levi et al, 2022). This study adsorbed CpG to the surface of the CP and OVA encapsulated or embedded between the CP structures.…”

“…Schematic of metal organic coordination polymers (CP) in one‐dimensional self‐assembly and metal–organic frameworks (MOF) in their two‐ and three‐dimensional self‐assembly (Eckshtain‐Levi et al, 2022)…”

“…CpG can be adsorbed on to the surface of CPs through a strong metal–phosphate bond (Z. Wang, Fu, et al, 2017) or by π–π interactions with an organic ligand (Y. Zhang, Liu, et al, 2017). Proteins with a His‐tag can allow for metal ion to protein complexation on the CP surface (Eckshtain‐Levi et al, 2022). One drawback to having the biomolecule surface attached is that it is exposed to the environment which can result in denaturation.…”

A Nanoparticle-Based Anticaries Vaccine Enhances the Persistent Immune Response To Inhibit Streptococcus mutans and Prevent Caries

“…Zhang et al prepared ZIF-8-based nanoparticles to target dendritic cells (DCs) and induce adequate immune responses as a method to provide a powerful platform against invasive malignancy and rechallenged tumors ( 19 ). In addition, ZIF-8 NPs were functionalized with poly(ethylene glycol) ( 20 ), aluminum ( 21 ), cytosine-phosphate-guanine oligodeoxynucleotides (CpG) ( 22 ), or peptides ( 23 ) that were utilized to encapsulate several antigens, such as tumor-associated antigens ( 24 ), bacterial antigens, or viruses ( 25 ), as a vaccine delivery system to enhance antigen-specific immune responses. However, few ZIF-8 NP-based adjuvants have been applied to encapsulate the PAc antigen from S. mutans to induce an immune response and protect against caries.…”