Particulate adjuvants increase vaccine immunogenicity and are included in a substantial portion of the multi-billion dollar global vaccine sector. Adjuvanted vaccines often require resuspension prior to administration and as formulation complexity increases in adjuvanted vaccines, understanding the mechanisms leading to challenges in resuspension is key to their furthered development. Our work starts with the study of a fundamental colloidal gel system through the introduction of one nonideality, particle bidispersity. We focus on translating particle level interactions to broader implications on the gelation state, mechanical stability, and aggregation kinetics. Confocal microscopy and 3D image processing tools were used to identify the particle interactions in mono- and bidisperse hard sphere-like colloids in order to analyze their pairwise interactions and local cluster architecture. Increasing the particle size disparity led to disordered, sub-isostatic networks that altered the distribution of tetrahedral motifs associated with the structural stability of these gels.
Our work highlights the relevance of these concepts to adjuvanted vaccines. Deviations from ideal structural arrangements and interactions lead to weakening of the sediment network structure and subsequent gel failure that leads to further compaction and eventual caking. To study these issues in vaccine adjuvants, we used a model system combining aluminum phosphate adjuvant with proteins of varying strength such as bovine serum albumin (BSA) and lysozyme in salt-free and saline (0 and 150 mM NaCl) conditions. Both rheological and confocal imaging techniques revealed that formulation nature strongly affected the failure state of the colloidal gel network. Lysozyme and protein-free formulations were found to introduce a loosely packed but stable gel that resuspended easily whereas BSA resulted in dense colloidal packings with a large subpopulation of denser aggregates that resulted in weaker rheological signal and increased difficulty in resuspension. Rheological testing further revealed that independent of formulation condition, this final packing fraction was the critical parameter in identifying resuspendability. These combined works highlight the critical role that the microstructural arrangement of adjuvants plays into its development in advanced vaccine platforms.
Research Interests
My doctoral studies have revolved strongly around the goal of correlating microstructural colloidal properties to their bulk properties and rheological parameters through imaging, fluorescent tagging, scattering, rheology, and coding. Incorporating process parameters through shear, flow, and sedimentation are necessary to understand full formulation phenomena. I also have a strong interest in taking complex experiments and extracting hidden high dimensionality data through image analysis, network models, and machine learning models. My current goal is to find a R&D position that allows me to combine both my wet lab and coding based skills to real world drug products to identify process and formulation optimizations in the downstream environment.