Enhancing Vaccine Stability and Immunogenicity Through Biomimetic Mineralization using Zeolitic-Imidazole Frameworks (ZIFs)

Vaccines are susceptible to structural conformational changes under environmental and chemical stressors, compromising their therapeutic efficacy. This lecture presents three innovative case studies that address this challenge to enhance the stability, preservation, and immunogenicity of protein, DNA, and lipid nanoparticle based vaccines.<br/>First, we discuss using zeolitic imidazolate framework-8 (ZIF-8) as a protective agent for a model viral vector against denaturing conditions. Immunoassay and spectroscopy analysis reveal that ZIF-8 provides enhanced thermal and chemical stability to the conformational structure of the encapsulated viral nanoparticle. Long-term biological activity studies in animal models demonstrate the integrity, biosafety, and immunogenicity of the virus-ZIF composite. Furthermore, histological analysis confirms the absence of tissue damage, highlighting ZIF-based protein composites as promising candidates for preserving proteinaceous drugs, ensuring biocompatibility, and controlling drug release in vivo.<br/>Next, we explore stabilizing proteoliposomes, supramolecular lipid-protein assemblies that mimic cellular membranes. We demonstrate that metastable lipid, protein-detergent, and protein-lipid complexes can be successfully immobilized within zeolitic-imidazole framework (ZIF) bio-composites. This immobilization strategy enhances their stability against chemical and physical stressors such as elevated temperatures, chemical denaturants, aging, and mechanical stresses. Extensive morphological and functional characterization confirms that the encapsulated complexes maintain their native morphology, structure, and activity, which would otherwise rapidly degrade without immobilization.<br/>Lastly, we address the pressing need for effective vaccines against pathogenic bacteria in the face of increasing antibiotic resistance. The genetic diversity of bacteria poses challenges in selecting appropriate antigens, hindering vaccine development. We present a proof-of-principle method to enhance the immunogenicity of a model pathogenic E. coli strain by forming a slow-releasing depot. Biomimetic mineralization within a metal-organic framework (MOF) effectively encapsulates the E. coli strain, enhancing antibody production and improving survival in a mouse bacteremia model. This approach surpasses the limitations of whole-cell formulations and demonstrates the potential for successful clinical translation.<br/>These innovative strategies utilizing ZIFs and MOFs hold great promise for revolutionizing vaccine design, preservation, and immunogenicity. By enhancing stability and ensuring effective immune responses, these advancements contribute to developing next-generation approaches for combating bacterial infections and preventing the spread of pathogens.<br/>REFERENCES:<br/>Luzuriaga MA, <i>et al. </i><u>Metal-Organic Framework Encapsulated Whole-Cell Vaccines Enhance Humoral Immunity against Bacterial Infection</u>. <i>ACS Nano</i>. <b>2021</b> Nov 23;15(11):17426-17438. DOI: 10.1021/acsnano.1c03092. PMID: 34546723.<br/>Herbert FC, <i>et al</i>. <u>Stabilization of supramolecular membrane protein-lipid bilayer assemblies through immobilization in a crystalline exoskeleton</u>. <i>Nat Commun</i>. <b>2021</b> Apr 13;12(1):2202. DOI: 10.1038/s41467-021-22285-y. PMID: 33850135; PMCID: PMC8044103.<br/>Luzuriaga MA, <i>et al</i>. <u>Enhanced Stability and Controlled Delivery of MOF-Encapsulated Vaccines and Their Immunogenic Response In Vivo</u>. <i>ACS Appl Mater Interfaces</i>. <b>2019</b> Mar 13;11(10):9740-9746. DOI: 10.1021/acsami.8b20504. PMID: 30776885.