Dr. Krishnendu Roy (Engineering, Vanderbilt University)

Committee Members:

Dr. Andres García (ME, Georgia Institute of Technology)

Dr. Erik Dreaden (BME, Georgia Institute of Technology)

Dr. Valeria Milam (MSE, Georgia Institute of Technology)

Dr. Susan M. Thomas (ME, Georgia Institute of Technology)

Utilizing Combinatory Adjuvant-Loaded Chitosan-Derived Nanoparticles for a Joint SARS-CoV-2/Influenza Vaccine

In the wake of the SARS-CoV-2 pandemic and the need for yearly vaccination for flu, there is an ever-growing demand for a single vaccine formulation that can target and immunize against both pathogens. While investigation is ongoing for joint vaccine candidates, the current focus has been mainly on the simultaneous administration of separate vaccines rather than a new hybrid vaccine design. In this work, we have designed and synthesized chitosan and chitosan-IAA-based nanoparticles to use as a platform for combinatorial delivery of multiple vaccine-adjuvants together with soluble delivery of flu and SARS-CoV-2 antigens. Specifically, we have used a combination of the TLR9 agonist CpG and the RLR agonist pUUC. In vitro testing in two distinct primary bone-marrow-derived antigen-presenting cell (APC) cultures demonstrated a strong cell-phenotype-dependent cytokine response to these nanoparticle systems. After administering these with SARS-CoV-2 and H5N1 influenza antigens in a dual-vaccine formulation, we confirmed high pathogen-specific antibody titers in serum and BAL fluid. Our results provide further insights into the impact of immune cell phenotype on vaccine responses and show promise for creating a novel joint subunit vaccine for two prevalent pathogens.