Coccidioidomycosis, also known as Valley Fever (VF) is caused by the fungus Coccidioides. Pigtail macaques (PTMs) bred at the Washington National Primate Research Center (WaNPRC) in Mesa, AZ are naturally infected with Coccidioides and are similar to humans in their physiology, symptoms, and immune responses. Populations with a weakened immune system, notably older individuals, are at risk for severe complications from infection. Additionally, there is evidence that males have a higher incidence of VF than females in endemic areas. I characterized the immune responses in a PTM model across age and sex to better understand how VF affects the immune response of these populations. Forty-two PTMs (2.25-19.24 years, 3.66-18.29 kg, 37 female, 5 male) at the WaNPRC were sampled for blood. The frequencies of immune cell subsets in whole blood were characterized by flow cytometry and compared for significant differences based on age and sex. I analyzed sex-based differences with Brown-Forsythe and Welch ANOVA t-tests and found no statistically significant differences. For age-based differences, we used a simple linear regression to analyze differences by age in immune cell subsets. We found that old PTMs (10.07-19.24 years) have higher activation of CD8+ T cells, myeloid dendritic cells, intermediate monocytes, and higher frequency of γΔ T cells and CD4+ γΔ T cells than young PTMs (2.25-9.69 years). Young PTMs have a higher frequency of CD45+ granulocytes, PD-1 High CD8+ T cells, plasmacytoid dendritic cells, and NK cells. By correlating older PTMs with higher immune cell activation, and younger PTMs with higher immune cell frequency, we have a better understanding of how a vaccine or treatment could be developed to support older individuals, who are at greater risk of severe infection.

Vaccines have successfully reduced global infectious disease burden, but there is room to improve vaccination technologies. Because many pathogens infect at mucosal sites, a goal of new vaccines is to promote strong mucosal and systemic antibody and T-cell responses. Integrated fiber microneedle devices (iFMN) are a novel oral vaccination method that may achieve this goal. These devices are patches with a polymer backfill matrix and multiple >1 mm pyramidal needles that penetrate immune cell-rich mucosal tissue in the mouth, inducing immune responses at draining lymph nodes. To test the hypothesis that priming with iFMN delivery of a DNA vaccine increases mucosal and systemic antibody responses after systemic booster immunization with the same vaccine, male rhesus macaques (n=6) were primed with an iFMN delivery of a DNA vaccine encoding Influenza A Virus (IAV) Nucleoprotein (NP) at weeks (0) and (6). The macaques then received a single boost of the same NP DNA vaccine at week (12) using the proven delivery modality of Gene Gun epidermal delivery (GG). Mucosal secretions (including bronchoalveolar lavage, saliva, and nasal/tracheal swabs) and serum were collected 2-4 weeks before and after each immunization. I conducted enzyme-linked immunosorbent assays (ELISAs) to quantify antigen-specific IgG and IgA binding antibody at each timepoint. To characterize the priming effect of iFMN oral delivery on systemic and mucosal antibody responses, I compared these animals’ responses to macaques (n=8) previously immunized with a single GG dose of the same NP DNA vaccine. The iFMN-primed animals had robust post-GG boost NP-specific IgG responses in serum but these responses were not significantly higher than for macaques boosted solely with GG DNA. These results demonstrate that iFMN delivery did not effectively prime for robust systemic and mucosal antibody responses. Additional experiments will be done to confirm these findings.

In response to the nuclear discharge incident on 21st August 2023 from the Fukushima nuclear reactors into the Pacific Ocean, Japan found itself at the forefront of a renewed global discourse on nuclear energy policy again post the 2011 Fukushima Daiichi accident. The consequential surge in antinuclear sentiment, particularly noteworthy within the East Asia region, serves as the impetus for this research, which seeks to meticulously analyze the potential impact of such sentiment on the public's perception of Japan's nuclear energy policy. This research adopts Akhiro Ogawa's conceptual framework of "anti-nuclear citizen" to scrutinize its influence on the youth demographic, and whether or not the identity influences their attitude towards Japan's current pro-nuclear policy. To ascertain empirical data, the survey method is employed to measure college youth’s sense of precarity, political involvement, and conscientiousness, serving as indicators of one’s alignment with the antinuclear citizen identity. The survey targets undergraduate Japanese exchange students and domestic students who are interested in Japanese studies at the University of Washington and undergraduate students in Japan and aims to delineate the nuanced correlations between antinuclear citizenship and specific policy perceptions. Recognizing the survey’s limitation of snowball sampling predicts a collective behavior that may not be representative of the general population, the study acknowledges potential biases and would like to serve as evidence to elucidate the presence or absence of “antinuclear citizens” within the defined focus group. Furthermore, the survey results are anticipated to delve into the rationales behind certain policy perceptions: generally anti-nuclear or pro-nuclear, leveraging participants' international experiences to augment the evidential support for the application of Ogawa's "antinuclear citizen" ideology. By analyzing the attitudes of the surveyed population toward Japan's nuclear policies, this research aspires to contribute to the conversation of the complex interplay between antinuclear sentiment, identity, and policy perceptions.