Filtering by
- Genre: Doctoral Dissertation
Vaccines are one of the most effective ways of combating infectious diseases and developing vaccine platforms that can be used to produce vaccines can greatly assist in combating global public health threats. This dissertation focuses on the development and pre-clinical testing of vaccine platforms that are highly immunogenic, easily modifiable, economically viable to produce, and stable. These criteria are met by the recombinant immune complex (RIC) universal vaccine platform when produced in plants. The RIC platform is modeled after naturally occurring immune complexes that form when an antibody, a component of the immune system that recognizes protein structures or sequences, binds to its specific antigen, a molecule that causes an immune response. In the RIC platform, a well-characterized antibody is linked via its heavy chain, to an antigen tagged with the antibody-specific epitope. The RIC antibody binds to the epitope tags on other RIC molecules and forms highly immunogenic complexes. My research has primarily focused on the optimization of the RIC platform. First, I altered the RIC platform to enable an N-terminal antigenic fusion instead of the previous C-terminal fusion strategy. This allowed the platform to be used with antigens that require an accessible N-terminus. A mouse immunization study with a model antigen showed that the fusion location, either N-terminal or C-terminal, did not impact the immune response. Next, I studied a synergistic response that was seen upon co-delivery of RIC with virus-like particles (VLP) and showed that the synergistic response could be produced with either N-terminal or C-terminal RIC co-delivered with VLP. Since RICs are inherently insoluble due to their ability to form complexes, I also examined ways to increase RIC solubility by characterizing a panel of modified RICs and antibody-fusions. The outcome was the identification of a modified RIC that had increased solubility while retaining high immunogenicity. Finally, I modified the RIC platform to contain multiple antigenic insertion sites and explored the use of bioinformatic tools to guide the design of a broadly protective vaccine.
The first paper is based on a systematic literature review where evidence from morphological mitigation strategies in HUDs were critically reviewed, synthesized and integrated. Metrics, measurements, and methods were extracted to examine the applicability of the different strategies, and a content synthesis identified the levels of strategy success. Collective challenges and uncertainties were interpreted to compare aspirational goals from actualities of morphological mitigation strategies.
The second paper unpacks the relationship of urban morphological attributes in influencing thermal conditions to assess latent magnitudes of heat amelioration strategies. Mindful of the challenges presented in the first study, a 92-day summer field-measurement campaign captured system dynamics of urban thermal stimuli within sub-diurnal phenomena. A composite data set of sub-hourly air temperature measurements with sub-meter morphological attributes was built, statistically analyzed, and modeled. Morphological mediation effects were found to vary hourly with different patterns under varying weather conditions in non-linear associations. Results suggest mitigation interventions be investigated and later tested on a site- use and time-use basis.
The third paper concludes with a simulation-based study to conform on the collective findings of the earlier studies. The microclimate model ENVI-met 4.4, combined with field measurements, was used to simulate the effect of rooftop shade-sails in cooling the near ground thermal environment. Results showed significant cooling effects and thus presented a novel shading approach that challenges orthodox mitigation strategies in HUDs.