Nearly four decades after HIV (Human Immunodeficiency Virus) was identified as the causal agent of the AIDS (Acquired Immunodeficiency Syndrome) pandemic, it remains a top global health concern impacting millions of people around the world particularly in Sub-Saharan Africa. Despite significant scientific, governmental and nongovernmental organizational efforts, most HIV-infected patients do not have access to prevention and treatment. Since cure is not available yet, developing a vaccine to prevent HIV from spreading is a priority. Previous studies have worked on an HIV vaccine platform using attenuated Vaccinia vector and plant-produced HIV virus-like particles (VLPs) to deliver Gag and dgp41 antigens as a heterologous prime-boost strategy. To further study this work, I conducted immunogenicity studies in rabbits which exhibited high IgG responses against Gag (p < 0.002) and less to dgp41. To increase the immunogenicity to dgp41, focusing on MPER, a combination of IgG fusions with VLPs as a vaccine platform was studied in mice. Both IgG fusion constructs showed similar serum results, though Gag-specific serum IgG responses were significantly higher (p < 0.007) for the recombinant immune complex (RIC) group than hexamer forming complexes (Hex). In an effort to expand the use of HIV VLPs, RSV (Respiratory Syncytial Virus) pre-fusion stabilized F (pre-F) protein was presented by self-assembling HIV-1 Gag as a potential vaccine strategy for RSV infections. Multiple constructs were designed to assemble into chimeric VLPs and tested for recombinant plant expression. Mouse immunogenicity study using these chimeric VLPs showed significantly high F-specific IgG (p < 0.001) in serum and superior IgA in mucosal samples for the group that received one of the pre-F stabilized VLP constructs. Moreover, when the same antigen was administered with cholera toxin intranasally, it generated IgA response in nasal flush higher than when it was administered subcutaneously. To summarize, this study showed the efficiency of a plant-produced VLP-based system as an adaptable chimeric vaccine platform for potential use with various viral antigens in pursuit of a vaccine strategy that is immunogenic in animal studies.

Quantifying and tracking viruses can be complicated for a number of reasons. Viruses can move rapidly through populations, leave little trace, or if a trace is left, be difficult to discern from similar viruses, and they can mutate within hosts to name a few. Lymphocytic choriomeningitis virus (LCMV) is a prime example of this, as it has many strains, however they segregate into acute and chronic viral variants based on a particular mutation. Described is a new methodology to identify LCMV infections in mice following viral clearance through differentiating antibody repertoire from serum on random peptide arrays. This technology was utilized to distinguish LCMV Arm and LCMV C-13 infections in mice, and also acute and chronic infections caused by low and high doses of LCMV C-13. Noonan syndrome is a hereditary disorder resulting in multiple physical impairments in afflicted patients as well as frequent neurological impairments. Multiple gene mutations can result in Noonan syndrome including the rapidly accelerated fibrosarcoma one (RAF1) gene, a gene critical in the rat sarcoma/mitogen activated protein kinase (RAS/MAPK) cell signaling pathway. The incidence of autoimmunity in patients with Noonan syndrome is estimated to be roughly 14% compared to 2-5% for an average population. As the RAS/MAPK is heavily involved with immune functions, characterizing the immune system in Noonan syndrome model mice could provide valuable insights. Mice expressing a Raf1L613V gain-of-function mutation were used to model Noonan syndrome in order to investigate the root cause of autoimmunity. Elevated numbers of splenocytes and thymocytes were found in the mutant mice compared to wild type mice. Also, higher rates of inflammatory cytokine production were found in cells from mutant mice infected with LCMV, particularly TNFa and IFNy, two hallmark cytokines in the pathogenesis of both SLE and Hashimoto thyroiditis, two commonly occurring autoimmune disorders in Noonan syndrome patients. This led to the hypothesis of autoreactive cells potentially escaping negative selection in the thymus which could be responsible for autoimmunity.