Grant: Project Grant

Modern vaccine development is largely moving towards sub-unit vaccines comprised of small molecules from pathogens that are the target of an effective immune response (referred to as antigen) together with accessory molecules that help stimulate the response (referred to as adjuvants), and are considered safer than whole pathogen vaccines. However, how these components should be formulated to elicit potent antigen-specific immunity remains an open question. B cells are the primary target of effective vaccines as they produce antibodies that aid in pathogen clearance. Previous studies have demonstrated that co-delivery of antigens and adjuvants using nanoparticles enhances B cell activation and antibody production. However, the precise spatial features of antigen and adjuvant presentation that optimizes B cell activation remain unclear, owing to limited synthetic flexibility of these nanomaterials. To address this challenge, we propose to array antigen and adjuvant on synthetic DNA nanostructures, which offer precise control over shape, molecular spacing, and number of molecules - enabling fabrication of designer nanostructures mimicking intact pathogens. We will investigate how these custom nanoscale features of antigen and adjuvant presentation maximize B cell activation and antibody production. Outcomes from this study will provide guidelines for effective vaccine design and targeted therapeutics against B cell mediated diseases.