Research Focus: Investigating the Underlying Mechanisms of the Immune Response to Chitosan-Derived Combinatory Adjuvant Nanoparticles for Vaccines.

Subunit vaccines are one of the more common and safer types of vaccine, using an antigen taken from a pathogen of interest (i.e. proteins or polysaccharides) in order to prime the body’s immune system in preparation for an encounter with the pathogen itself. However, there is constant need for improvement in subunit vaccine efficacy, as these vaccines depend on immunostimulatory adjuvants to make a fully “memorable” impression and entice antibody production. For this reason, my research is that in the field of combinatory adjuvants for vaccine design, utilizing multiple nucleic acid agonists that target specific immune pathways in tandem to broaden the response to said vaccines or produce otherwise synergistic effects.
The method of adjuvant delivery also plays a strong role in the response to such a vaccine; proper adjuvant and antigen delivery tends to depend on the pathogen-like particle that said molecules are a part of. Chitosan serves as both a means to create positively charged nanoparticles as well as a STING agonist in of itself, further bolstering the potential response to these vaccine systems. Furthermore, through modifying chitosan with functional molecules like imidazole-acetic acid (IAA), certain desirable attributes, such as endosomal escape and enhanced mucosal delivery.
My current research aims to apply these particle systems to SARS-CoV-2. I will be examining both intranasal and intramuscular routes of administration to determine which route produces an optimal vaccine response. As for prior, in vitro work, I have measured the response of these particles in both GM-CSF and FLT3L bone marrow cultures, identifying synergies between several adjuvants in tandem and the differences between each cell culture method’s primary pathway for cytokine secretion.

Relevant Publications:

• Pradhan, P., Toy, R., Jhita, N., Atalis, A., Pandey, B., Beach, A., Blanchard, E. L., Moore, S. G., Gaul, D. A., Santangelo, P. J., Shayakhmetov, D. M., & Roy, K. (2021). TRAF6-IRF5 kinetics, TRIF, and biophysical factors drive synergistic innate responses to particle-mediated MPLA-CpG co-presentation. Science Advances, 7(3). https://doi.org/10.1126/sciadv.abd4235
• Atalis, A., Keenum, M. C., Pandey, B., Beach, A., Pradhan, P., Vantucci, C., O’Farrell, L., Noel, R., Jain, R., Hosten, J., Smith, C., Kramer, L., Jimenez, A., Ochoa, M. A., Frey, D., & Roy, K. (2022). Nanoparticle-delivered TLR4 and RIG-I agonists enhance immune response to SARS-CoV-2 subunit vaccine. Journal of Controlled Release, 347, 476–488. https://doi.org/10.1016/j.jconrel.2022.05.023
• Toy, R., Pradhan, P., Ramesh, V., di Paolo, N. C., Lash, B., Liu, J., Blanchard, E. L., Pinelli, C. J., Santangelo, P. J., Shayakhmetov, D. M., & Roy, K. (2019). Modification of primary amines to higher order amines reduces in vivo hematological and immunotoxicity of cationic nanocarriers through TLR4 and complement pathways. Biomaterials, 225, 119512. https://doi.org/10.1016/j.biomaterials.2019.119512