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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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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.
