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Influenza is a seasonal acute respiratory infection, causing millions of illnesses worldwide on a yearly basis. A common subtype, the influenza A virus (IAV), is a single stranded RNA virus, that similarly to other subtypes, targets epithelial cells. The best way to protect against the virus is through vaccination. Vaccine induced protection is mediated through the generation of adaptive CD4 and CD8 T cells, as well as antibody producing B Cells. Although generally thought of as helper cells, previous research has highlighted additional roles of memory CD4 T cells in mediating protection against IAV beyond their helper function. More specifically they have been shown to enhance innate inflammatory responses and facilitate the recruitment of innate cell populations; including a recently discovered population of Innate Lymphoid Cells (ILC). Previous research has shown ILCs to have a key role in tissue repair and limiting tissue damage following infection. Whether memory cell response, during protective recall, modulates ILC repair function is currently not well understood. To better understand the possible regulation of ILCs by memory cells, we utilized a molecular technique called reverse transcription polymerase chain reaction (RT-qPCR), to assess select innate lymphoid cell associated protein expression following IAV challenge and rechallenge. We hypothesize, that memory cells drive differential expression of ILC associated repair proteins to assist in a faster and more efficient mobilization of repair processes following pathogenic invasion. Our goal is to highlight and better understand the regulatory and inflammatory responses memory cells provide following viral infection, as these may lead to key steps in the development of long lasting and efficacious vaccines.

The COVID-19 pandemic has been an ongoing disaster that has devasted millions of lives. With the development of COVID-19 vaccines in late 2020, there was a potential for populations to gain artificial active immunity in order to prevent future outbreaks. However, despite successful clinical trials, millions of citizens have been hesitant to receive the COVID-19 vaccines (Khubchandani et al., 2021). Demographics of the most prominent US vaccine-hesitant populations consist of ethnic/racial minorities and Republicans groups (Khubchandani et al., 2021). Little information is known about COVID-19 vaccine hesitancy in colleges and universities. Colleges provide an elevated risk for infection through their communal residencies, the reemergence of campus activities, and continuous travel to home (Sharma et al., 2021). This study explored COVID-19 vaccine hesitancy in UCF college students and explored potential pathways to achieve higher vaccination rates. Potentially believed COVID-19 misinformation was also studied. A COVID-19 opinion survey was designed and distributed to the UCF college population. Two hypotheses were made for this study: (1) There is a significant effect on vaccination status among people of different political parties, field of study, living conditions, masking frequency, and scores on the knowledge-based questions portion. (2) There will be a significant effect on knowledge-based scores with political party and field of study. The results were analyzed using Chi-square, one-way ANOVA, or two-way ANOVA on SPSS. The results showed a significant effect on vaccination status in political parties, masking frequency in class, and scores on the knowledge-based survey questions. There was no significance with race/ethnicity and field of study. There was a significant effect on the knowledge-based survey questions with political party and field of study. Potential side effects and the vaccines being seen as ineffective were the top two reasons that students choose not to vaccinate.

Influenza is a severe disease in humans and animals, causing upwards of 40,000 deaths every year in America alone. Influenza A virus (IAV) also causes periodic pandemics every 10 to 50 years, killing millions of people. Despite this, very few effective therapies are available. All strains of IAV are prone to developing resistance to antibodies due to the high mutation rate in the viral genome. Because of this mutation rate, a yearly vaccine must be generated before every flu season, and efficacy varies year to year. IAV has also mutated to escape several of the clinically-approved small molecule inhibitors. A therapeutic agent that targets a highly conserved region of the virus could bypass resistance and also be effective against multiple strains of IAV. IAV attachment is mediated by many individually weak hemagglutinin–sialic acid interactions that all together make a strong attachment to a host cell. Polymerized sialic acid analogs can recreate these interactions and block infection. However, they are not ideal therapeutics due to solubility issues and in vivo toxicity. We used liposomes as a novel means for delivery of the sialic acid-containing glycan, sialylneolacto-N-tetraose c (LSTc). LSTcbearing decoy liposomes form multivalent, polymer-like interactions with IAV. Decoy liposomes competitively bind IAV in hemagglutination inhibition assays and inhibit infection of target cells in a dose-dependent manner. LSTc decoy liposomes co-localize with IAV, while control liposomes do not. Inhibition is specific, as inhibition of Sendai virus and respiratory syncytial virus is not observed. In contrast, monovalent LSTc does not bind IAV or inhibit infectivity. LSTc decoy liposomes prevent the spread of IAV during multiple rounds of replication in vitro and extend survival of mice challenged with a lethal dose of virus. Considering the conservation of the hemagglutinin binding pocket and the ability of decoy liposomes to form high-avidity interactions with IAV hemagglutinin, our decoy liposomes have potential as a new therapeutic agent against emerging strains.

While memory CD4 T cells are critical for effective immunity to pathogens, the mechanisms underlying their generation are poorly defined. Although extensive work has been done to examine the role of antigen (Ag) in shaping memory formation, most studies focus on the requirements during the first few days of the response known as the priming phase. Little is known about whether or not Ag re-encounter by effector T cells (late Ag) alters CD4 memory T cell formation. Since influenza infection produces a large, heterogeneous, protective CD4 memory T cell population, I used this model to examine the role of late Ag in promoting CD4 memory T cell formation. In the experiments presented in this thesis, I demonstrate that late Ag is required to rescue responding CD4 T cells from default apoptosis and to program the transition to long-lived memory. Responding cells that failed to re-encounter Ag had decreased memory marker expression and failed to produce multiple cytokines upon re-stimulation. Ag recognition is required at a defined stage, as short-term Ag presentation provided 6 days after infection is able to restore canonical memory formation even in the absence of viral infection. Finally, I find that memory CD4 T cell formation following cold-adapted influenza vaccination is boosted when Ag is administered at this stage. These findings imply that persistence of viral Ag presentation into the effector phase is the key factor that determines the efficiency of memory generation. They also suggest that administering Ag during the effector stage may improve vaccine efficacy.