Engineered Proteinaceous Materials and, Their Applications in Vaccine Development

Recent advancements in immunotherapy and vaccinology have exploited recombinant proteins and inactivated whole organisms to replace live-attenuated pathogens, which are typically used as immunogenic agents. Structural stability of these plays a pivotal role in efficient antigen presentation to major histocompatibility complexes (MHC). Processing of antigenic peptides by MHC is an important factor in stimulation of strong immune responses. Unfortunately, most proteinaceous materials and inactivated whole organisms undergo significant structural changes during vaccine development, leading to poor antigen presentation, and eliciting low immunogenicity in vivo. Despite years of effort to improve stability of proteinaceous materials, only a few of approaches exist, and development of methods to increase their structural stability and guarantee their proper antigen presentation in vivo are still needed. In this work, we demonstrate that coordination polymers formed through the interlinking of organic ligands and metal centers, can help overcome the structural stability issues related to proteinaceous materials. Our methods not only provide structural stability in vitro but have also shown immunogenicity improvement when tested in vivo. The first chapter reviews the concept of supramolecular self-assembly, process by which materials with different physiochemical properties can be obtained. Virus-like particles are then introduced, and several different applications of these briefly discussed. The second chapter describes an innovative method for construction of near-infrared particles used for non-invasive imaging in vivo. The resulting composites show great promise as candidates for in vitro cellular and deep tissue imaging in vivo. The third chapter elaborates on the stabilization of liposomes, transmembrane proteins, and proteoliposomes through their encapsulation in zeolitic-imidazolate frameworks. The resulting composites show enhanced stability against harsh conditions (e.g., high temperatures, mechanical stress, and denaturing agents). The fourth chapter reviews commonly used polymer-based materials for vaccine development. Further, it elaborates on the rationale behind the utilization of such materials and discusses some of the current obstacles faced by in the vaccine manufacturing field. It concludes with a perspective on technologies that could help the field overcome such obstacles. The fifth chapter introduces the fabrication of whole-cell vaccines against bacterial infections using metal-organic frameworks. It systematically presents details about the synthesis, in vitro assessment, and in vivo testing of the vaccine against uropathogenic E. coli. The sixth chapter shows the generalizability of metal-organic frameworks to produce whole vaccines using different types of bacterial strains. It presents the importance of different T-cells for proper development of immunity against recurrent urinary tract infections and how ZIF-8 based vaccines can successfully recruit such cells.