Metal–Organic Coordination Polymer for Delivery of a Subunit Broadly Acting Influenza Vaccine
Meital Eckshtain‐Levi, Cole J. Batty, Liubov M. Lifshits, Brandon McCammitt, Kathryn M. Moore, Eva A. Amouzougan, Rebeca T. Stiepel, Eliza Duggan, Ted M. Ross, Eric M. Bachelder, Kristy M. Ainslie
Abstract
A zinc-carnosine (ZnCar) metal–organic coordination polymer was fabricated in biologically relevant N-(2-hydroxyethyl)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.