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.

Insect pheromones are crucial for survival and reproduction because they influence insect behavior, communication, and interactions within and outside the colony. Honey bees (Apis mellifera) have one of the most complex pheromonal communication systems. One pheromone, known as Queen Mandibular Pheromone (QMP), is released by the queen bee to regulate physiology, behavior, and gene expression in the female worker caste. The pheromone acts as a signal of queen presence that suppresses worker reproduction. In the absence of reproduction, young workers focus on taking care of the queen and larvae, known as nurse tasks, while older workers forage. In nurse bees, QMP has fundamental physiological impacts, including increasing abdominal lipid stores and increasing the protein content of hypopharyngeal glands (HPG). The HPG are worker-specific glands that can synthesize royal jelly used in colony nourishment. In workers, larger HPG signifies the ability to secrete royal jelly, while shrunken glands are characteristic of foragers that do not make jelly. While it is known that QMP increases abdominal lipid stores, the underlying mechanism is unclear: Does the pheromone simply make workers consume more pollen which provides lipids and protein, or does QMP also increase lipogenesis? In this study, I measured abdominal lipogenesis as fatty acid synthase (FAS) activity and monitored abdominal protein content and HPG size in caged, nurse-aged worker bees. In cages, workers were exposed to QMP or not, and they were provided with a lipid less diet in a full factorial design experiment. I found that QMP did not influence abdominal FAS activity or protein, but significantly increased HPG size. The data also revealed a significant positive correlation between abdominal protein and HPG size. My results do not support the idea that QMP modulates lipogenesis in worker bees, but my data can be interpreted to reflect that QMP mobilizes abdominal protein for the production of jelly in the HPG. This finding is in line with a previous study revealing a role of honey bee Brood Pheromone in mobilization of a major protein used in jelly production. Overall, my results support a fundamental role of QMP in worker metabolic processes associated with colony nourishment.

Heart disease is the leading cause of death in the developed world and often occurs following myocardial infarction. Apelin is an endogenous prepropeptide that has been studied for its role in improving cardiac contractility and vasodilation but suffers from a short half-life in the body. By encasing apelin in a nanoparticle patch, we were able to slowly release apelin to cardiac tissue and observe its effects for one month following induced myocardial infarction surgery in mice. This study demonstrates that the apelin nanoparticles can protect the heart from myocardial-induced heart failure, observing overall improved cardiac function and reduction of fibrotic scarring associated with post-myocardial infarction compared to a nontreated group.

Platelet Rich Plasma (PRP) is an emerging procedure in regenerative medicine that offers a non-surgical minimally invasive way for tissue repair and regeneration. PRP has many different bioactive molecules that are able to influence and help achieve greater recovery and regenerative outcomes. Diet has many effects on platelets and looking at the mechanism in which platelet function and aggregation are affected with different diets shows how they are able to affect PRP therapy. Looking at these mechanisms allows for better physician recommendations for preprocedural diets to optimize efficacy. This paper conducts a systematic review to investigate the influence that diet can have on PRP outcomes. It was shown that high fat diets lower the efficacy of treatment while the Mediterranean diet helps promote platelet function and help efficacy. The future is to look at more diets while also integrating lifestyle choice before treatment for optimal outcomes.