Auburn Research Day 2022

Vasilis C. Pliasas* 1 , Zach Menne* 2 , Virginia Aida 1 , Ji-Hang Yin 1 , Maria C. Naskou 1 , Peter J. Neasham 1 , J. Fletcher North 1 , Dylan Wilson 1 , Sheniqua Glover 1 , Ioanna Skountzou 2 , Constantinos S. Kyriakis 1,3 1 Department of Pathobiology, College of Veterinary Medicine, Auburn University; 2 Department of Microbiology and Immunology, Emory University, Atlanta; 3 Center for Vaccines and Immunology, University of Georgia B i omed i ca l Resea rch | Gr adua te/Undergr adua te St udent Clinical and Immunological Features of Protection Induced by an Influenza Neuraminidase Virus-Like Particle Vaccine After a Heterologous Influenza Infection 42

Influenza A virus (IAV) poses a perennial threat to both human and animal health. Seasonal influenza outbreaks and the potential of the emergence of novel zoonotic IAV necessitate the development of a broadly protective influenza vaccine. Commercial IAV vaccines target predominantly Hemagglutinin (HA)-specific epitopes resulting in the elicitation of less potent protection against heterologous strains. Neuraminidase (NA), the second most immunogenic IAV protein after HA, has been widely overlooked in commercial vaccine formulations despite its potential to induce broad heterologous immune responses. The objectives of this study were to assess the immunogenicity and protective efficacy of a recently developed N2 VLP vaccine platform in the swine model as a broadly protective influenza vaccine. A total of 18 influenza-seronegative piglets were used in the study. They were divided into 3 groups and were

prime-boost vaccinated with a 3-weeks interval with the N2 VLP vaccine, containing the NA protein from the A/Perth/16/2009 (H3N2), a commercial swine IAV vaccine, or adjuvant only, respectively. Pigs were intranasally challenged four weeks post-boost with A/ swine/NC/KH15/2016, an H3N2 swine IAV field isolate. Amino acid homology between the vaccine and challenge NA was 90.9%. Vaccine-induced protection was evaluated based on five parameters, (i) cellular immune responses, (ii) cytokine profile at euthanasia (day 5), (iii) virus titers in tissue homogenate samples, (iv) Bronchoalveolar lavage fluid (BALF) cytology, and (v) respiratory histopathology. While neither vaccine elicited complete protection, the NA VLP construct performed comparably to the commercial vaccine and significantly reduced pulmonary virus titers, BALF neutrophilic infiltration, and pulmonary histopathology compared to unvaccinated controls.

Cl i n i ca l Case Repor t | Med i ca l St udent A Review of Diagnostic Protocols and Patient Presentation of Nieman Pick Disease Type C 43

Background: Nieman-Pick Disease (NPD) is a group of rare metabolic disorders where the body does not store lipids properly and causes an accumulation of lipids in areas such as the brain. There are four types of the disease, Type A, B, C1, and C2. Types C1 and C2 (NPC) are due to the NPC1 and NPC2 genes. Patients with NPC present with neurological symptoms characteristic of neurodegenerative diseases, particularly early-onset Alzheimer's, including myoclonus, ataxia, dystonia, cognitive deficits, and psychiatric issues. Methods: A review of 6 research articles. 1 article distinguishes NPC from early-onset Alzheimer's dementia, 1 study evaluates cognitive rehabilitation of patients with NPC, 1 study explores potential biomarkers of NPC, 2 articles on the clinical presentation of NPC, and 1 article adds to the disease's pathogenesis and potential therapeutic approach, Results: A study showed possible ways to differentiate NPC and early-onset Alzheimer's disease in a clinical setting. They found that the main distinguishing factor in neurocognitive testing was how NPC patients had relatively preserved verbal memory. This shows that although the two ailments are similar in presentation, key differences should be considered when formulating a treatment plan for NPC patients. Another addition to the diagnostic protocol could be the use of biomarkers, as a study showed NPC patients had significantly decreased heat shock protein 70 (HSP70) levels and increased cholestane-triol levels compared to healthy controls. As far as treatment, cognitive rehabilitation is crucial for neurogenerative Anna Siddiq; David Stephen, DO Via Edward College of Osteopathic Medicine – Auburn Campus

diseases, as they prolong the ability of individuals to remain independent and with a higher quality of life, as one study showed. Psychiatric Illness can manifest at any stage or type of NPD. A case study showed a patient with juvenile NPC who presented with psychosis. The drug miglustat, typically for treating patients with the metabolic Gaucher Disease Type I, seemed to reverse the psychosis of juvenile NPC. This treatment of psychosis is important because the most frequently reported type of symptom in NPC is psychiatric symptoms. However, a study showed that movement disorders might have been overlooked in early diagnosis and treatment as they saw that myoclonus presented at a higher rate in their cohort compared to other cohorts. A potential novel therapeutic approach deals retromer impairment as a very recent study demonstrated that retromer dysfunction might have a vital role in the pathogenesis of NPC because mice with NPC1 mutations showed changes in the retromer distribution while the mice were pre-symptomatic compared to the control group. These studies provide grounds for further investigation on determining the best ways to diagnose and treat NPC. Conclusion: There is an indication of more research on how to distinguish NPC from other neurogenerative diseases through a more solidified diagnostic protocol and more definitive treatment to improve quality of life. More research on treatments is also needed, such as a possible novel therapeutic approach dealing with retromer impairment and more research on the benefits of miglustat in psychosis treatment. This need for advancement in diagnostic and treatment protocols is imperative as there is no cure for NPC.

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