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.

Many coastal cities around the world are becoming increasingly vulnerable to natural disasters, particularly flooding driven by tropical storm and hurricane storm surge – typically the most destructive feature of these storms, generating significant economic damage and loss of life. This increase in vulnerability is driven by the interactions between a wide number of complex social and climatic factors, including population growth, irresponsible urban development, a decrease in essential service provision, sea level rise, and changing storm regimes. These issues are exacerbated by the short-term strategic planning that dominates political action and economic decision-making, resulting in many vulnerable coastal communities being particularly unprepared for large, infrequent storm surge events. This lack of preparedness manifests in several ways, but one of the most visible is the lack of comprehensive evacuation and rescue operation plans for use after major storm surge flooding occurs. Typical evacuation or rescue plans are built using a model of a region’s intact road network. While useful for pre-disaster purposes, the immediate aftermath of large floods sees enormous swaths of a given region’s road system flooded, rendering most of these plans largely useless. Post-storm evacuation and rescue requires large amounts of atypical travel through a region (i.e., across non-road surfaces). Traditional road network models (such as those that are used to generate evacuation routes) are unable to conceptualize this type of transportation, and so are of limited utility during post-disaster scenarios. To solve these problems, this dissertation introduces an alternative network conceptualization that preserves important on-network information but also accounts for the possibility of off-network travel during a disaster. Providing this in situ context is necessary to adequately model transportation through a post-storm landscape, one in which evacuees and rescuers are regularly departing from roads and one in which many roads are completely interdicted by flooding. This modeling approach is used to automatically generate routes through a flooded coastal urban area, as well as to identify potentially critical road segments in advance of an actual storm. These tools may help both emergency managers better prepare for large storms, and urban planners in their efforts to mitigate flood damage.

Environmental heat is a growing concern in cities as a consequence of rapid urbanization and climate change, threatening human health and urban vitality. The transportation system is naturally embedded in the issue of urban heat and human heat exposure. Research has established how heat poses a threat to urban inhabitants and how urban infrastructure design can lead to increased urban heat. Yet there are gaps in understanding how urban communities accumulate heat exposure, and how significantly the urban transportation system influences or exacerbates the many issues of urban heat. This dissertation focuses on advancing the understanding of how modern urban transportation influences urban heat and human heat exposure through three research objectives: 1) Investigate how human activity results in different outdoor heat exposure; 2) Quantify the growth and extent of urban parking infrastructure; and 3) Model and analyze how pavements and vehicles contribute to urban heat.

In the urban US, traveling outdoors (e.g. biking or walking) is the most frequent activity to cause heat exposure during hot periods. However, outdoor travel durations are often very short, and other longer activities such as outdoor housework and recreation contribute more to cumulative urban heat exposure. In Phoenix, parking and roadway pavement infrastructure contributes significantly to the urban heat balance, especially during summer afternoons, and vehicles only contribute significantly in local areas with high density rush hour vehicle travel. Future development of urban areas (especially those with concerns of extreme heat) should focus on ensuring access and mobility for its inhabitants without sacrificing thermal comfort. This may require urban redesign of transportation systems to be less auto-centric, but without clear pathways to mitigating impacts of urban heat, it may be difficult to promote transitions to travel modes that inherently necessitate heat exposure. Transportation planners and engineers need to be cognizant of the pathways to increased urban heat and human heat exposure when planning and designing urban transportation systems.