Georgia Institute of Technology Materials Science and Engineering

Advisor:

Dr. Krishnendu Roy, Ph.D., Department of Biomedical Engineering, Georgia Institute of Technology and Emory University

Committee Members:

Dr. Andrés García, Ph.D., School of Mechanical Engineering, Georgia Institute of Technology

Dr. Erik Dreaden, Ph.D., Department of Biomedical Engineering, Georgia Institute of Technology and Emory University

Dr. Valeria Milam, Ph.D., School of Materials Science and Engineering, Georgia Institute of Technology

Dr. Susan N. Thomas, Ph.D., School of Mechanical Engineering, Georgia Institute of Technology

Investigating the Underlying Mechanisms of the Immune Response to Chitosan-Derived Combinatory Adjuvant Nanoparticles

The two critical components of subunit vaccines are antigen and adjuvant selection, the former specific to the pathogen, the latter specific to the desired immune response. One of the most used adjuvants is alum, a general-purpose adjuvant comprised of various aluminum salts that can form particle-like complexes with antigen. As this type of adjuvant continues to be widely used, there is a continual gap in knowledge about adjuvants that target more specific, individual pathways of the immune system, especially when used in tandem. From its role as a STING agonist, to its electrostatic methods of adsorbing other adjuvants, chitosan is a very similar material to alum for this application. Furthermore, this shellfish-derived protein also can be further modified with imidazoleacetic acid (IAA) for the purpose of facilitating endosomal escape and lowering toxicity. This research proposal aims to investigate the response to administering chitosan nanoparticles, both with and without IAA modification, loaded with other, more specific adjuvants to better understand the underlying mechanisms therein. By using two common murine bone marrow-derived cell culture methods, we have shown that differences in cell culture environment can affect this response, even demonstrating a complete pathway shift for type I interferon secretion. In terms of future in vivo studies, the viability of these particles as a vaccine towards a pathogen of therapeutic interest will be assessed, alongside the molecular mechanisms of the resulting immune response and biodistribution. Through this research, we hope to further knowledge on the topic of combinatorial adjuvants, while also presenting a viable alternative to alum as an electrostatically driven adjuvant particle system for vaccines.