Immunology and Infectious Disease Commons^™

A Ferritin Nanoparticle-Based Zika Virus Vaccine Candidate Induces Robust Humoral And Cellular Immune Responses And Protects Mice From Lethal Virus Challenge, Aryamav Pattnaik, Bikash R. Sahoo, Lucas R. Struble, Gloria E. O. Borgstahl, You Zhou, Rodrigo Franco, Raul G. Barletta, Fernando A. Osorio, Thomas M. Petro, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

The severe consequences of the Zika virus (ZIKV) infections resulting in congenital Zika syndrome in infants and the autoimmune Guillain–Barre syndrome in adults warrant the development of safe and efficacious vaccines and therapeutics. Currently, there are no approved treatment options for ZIKV infection. Herein, we describe the development of a bacterial ferritin-based nanoparticle vaccine candidate for ZIKV. The viral envelope (E) protein domain III (DIII) was fused in-frame at the amino-terminus of ferritin. The resulting nanoparticle displaying the DIII was examined for its ability to induce immune responses and protect vaccinated animals upon lethal virus challenge. Our results show that …

The Regulation Of Autoimmunity Genes In Pancreatic Β-Cells By Nf-Κb, Thomas Malone Martin

LSU Doctoral Dissertations

Type 1 diabetes (T1D) is an autoimmune disease where the immune system targets the pancreatic islet beta-cells, which are responsible for insulin production and secretion, leading to a state of insulin insufficiency. Many of the molecular details of disease onset and progression remain poorly understood, including key aspects of cytokine signaling. Therefore, we have examined some of the consequences of inflammatory cytokine signaling as a critical module relevant to T1D. Using interleukin-1 (IL-1) signaling as a well-defined paradigm for inflammation, we investigated key components of this signaling pathway in pancreatic beta-cells. We identified ICAM-1, one of the proteins expressed in …

A Diverse Flea (Siphonaptera) Assemblage From The Small Mammals Of Central New Mexico, Dianne E. Peterson, Jonathan L. Dunnum, Schuyler W. Liphart, Karen A. Boegler, Ralph P. Eckerlin, Eric P. Hoberg, Martha O. Perez-Arriaga, Katrina Derieg, David Garnand, Mariel L. Campbell, Joseph A. Cook

MANTER: Journal of Parasite Biodiversity

The geographical ranges of many mammals and their associated parasites are dynamic. Comprehensive documentation of these communities over time provides a foundation for interpreting how changing environmental conditions, driven by accelerating climate change, other anthropogenic disturbances, and natural events, may influence host-parasite interactions. Fleas (Order Siphonaptera) are obligate, hematophagous parasites of birds and mammals with medical interest because of their role in transmitting pathogens. From 2016 to 2019, we sampled the small mammal and associated flea communities in El Malpais National Conservation Area (El Malpais) in Cibola County, New Mexico. Among 898 mammalian specimens, 925 fleas representing 29 species were …

The Effect Of Bisphenol A (Bpa) Substitutes On Cd4+ T Cell Immunity, Cassandra Poole

Longwood Senior Theses

CD4+ helper T cells are an important cell of the immune system. One key factor in the mediation of the immune system in general, and T cells in particular, is the female sex hormone estrogen. Abnormal estrogen levels are associated with a variety of conditions, including autoimmune diseases, and several types of cancer, including breast cancer. BPA is a well-known estrogen mimicking compound, used in the manufacturing of plastics, epoxy resins, and polystyrenes. As the negative effects of BPA become more apparent, many BPA substitutes have been developed. While the effect of estrogen on T cells is understood, the effect …

Cell-Typing And Interaction Analysis Of The Immune Compartment Of The Tumor Microenvironment Using High-Resolution Omics Modalities, Courtney Taylor Schiebout

Dartmouth College Ph.D Dissertations

Single-cell RNA-sequencing (scRNA-seq) has provided a new frontier for the investigation of complex tissues. One ideal candidate for the utilization of this method is the tumor microenvironment (TME). The TME is often host to a complex set of cell populations and behaviors that can be highly influential for cancer inhibition or progression. This is especially true of the immune compartment of the TME: the presence of certain types of immune cells in the TME and their expression profiles can significantly affect cancer prognosis in some cases. By providing individual cell-level gene expression data, scRNA-seq can be highly informative for characterizing …

The Effects Of Specialized Pro-Resolving Mediator Lipoxin A4 On Pseudomonas Aeruginosa Biofilms And Interactions With Monocytes, Julianne M. Thornton

Graduate School of Biomedical Sciences Theses and Dissertations

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen known as a major cause of hospital-acquired secondary infections, commonly causing chronic respiratory infections in immunocompromised individuals, especially those with cystic fibrosis, and often found in wound infections. P. aeruginosa uses the quorum sensing pathway to readily form protective biofilms, which reduce the efficacy of antibiotics and access by host immune cells to eradicate the pathogen. Specialized pro-resolving mediators (SPMs) are lipids endogenously produced by the host immune response to infection to aid in infection resolution. One SPM, Lipoxin A4 (LxA4), has been shown to be a robust quorum sensing inhibitor.

The …

Investigating The Antibacterial And Immunomodulatory Properties Of Lactobacillus Acidophilus Postbiotics, Rachael M. Wilson

Graduate School of Biomedical Sciences Theses and Dissertations

Probiotics are nonpathogenic microorganisms that have been extensively studied for their ability to prevent various infectious, gastrointestinal, and autoimmune diseases. The mechanisms underlying these probiotic effects have not been elucidated. However, we and other researchers have evidence suggesting that probiotic bacteria secrete metabolites that are antimicrobial and anti-inflammatory. As such, we developed a methodology to collect the secreted metabolites from a probiotic bacterium, Lactobacillus acidophilus, and tested this cell free filtrate (CFF) both in vitro and in vivo. Using this CFF, we have demonstrated that L. acidophilus secretes a molecule(s) that has specific bactericidal activity against the opportunistic pathogen, Pseudomonas …

Mirna-489 Induces Immunogenic Cell Death In Triple Negative Breast Cancer Cells, Ryan P. Titus

Senior Theses

It has been well established that microRNAs (miRNAs) play an important role in the regulation of gene expression and consequently promoting or downregulating molecular pathways. When dysregulated, miRNAs have been found to serve as important biomarkers for cancer diagnosis and influence tumor initiation and progression. It has been previously established that miRNA-489 is a tumor suppressor microRNA, and it directly targets cell proliferative pathways like the HER2-SHP2-MAPK pathway. In this study, we focus on the role of miRNA-489, in the induction of immunogenic cell death (ICD) in triple-negative breast cancer cell lines. We first examined the effects of miRNA-489 on …

Prevalence Of Sars-Cov-2 Antibodies In Liberty University Student Population, Emily Bonus

Senior Honors Theses

In 2020, the virus SARS-CoV-2 gained attention as it spread around the world. Its antibodies are poorly understood, and little research focuses on those with few COVID-19 complications yet large numbers of close contacts: university students. This longitudinal study recorded SARS-CoV-2 antibody presence in 107 undergraduate Liberty University students twice during early 2021. After extensive data cleaning and the application of various statistical tests and ANOVAs, the data seems to show that in the case of COVID-19 infections, SARS-CoV-2 IgM antibodies are immediately produced, and then IgG antibodies follow later. However, the COVID-19 vaccine causes the production of both IgM …

Potentiation Of The Immune Checkpoint Blockade Response By Metabolic Modulation Is Predictable Using Molecular Imaging, Renee L. Chin

Dissertations & Theses (Open Access)

Unregulated cell division is a hallmark of cancer. The high metabolic needs of the tumor cells result in nutrient depletion and produce a hostile tumor microenvironment (TME) for antitumor immune cells, protecting the tumor from immune cell-mediated control and immunotherapy. Two of these environmental factors, acidosis and hypoxia, are commonly found in solid cancers. In my thesis, I posited that modulation of tumor acidosis and hypoxia can serve as biomarkers by indicating immunogenicity and tumor sensitivity to immune checkpoint blockade (ICB) as monitored using molecular imaging. Esomeprazole was found to promote tumor immunogenicity and induce tumor control when used to …

Mir125a As Molecular Target Of Vitamin D Mediated Inhibition Of Cd4+ T Cell Differentiation Into Th17 Cells In Mrl/Lpr Lupus-Prone Mice, Miranda Hilt

Undergraduate Distinction Papers

The dynamic function of vitamin D in an array of immunomodulatory and anti-inflammatory mechanisms and its implication in the pathogenesis of autoimmune diseases has been the topic of much recent scholarship. Here I attempt to elucidate the molecular mechanism of vitamin D-mediated inhibition of the differentiation of CD4+ T cells into pro-inflammatory Th17 cells in MRL/lpr lupus prone mice by investigating how miR-125a expression is affected by dietary modulation of cholecalciferol (vitamin D₃). MRL/MpJ and MRL/lpr mice were split into three experimental groups and fed specially formulated diets that varied in their concentrations of vitamin D. …

Intergenerational Change In Hiv/Aids-Related Stigma In Cato Manor, Mijin Cho

Independent Study Project (ISP) Collection

In South Africa, the world’s epicenter of the HIV/AIDS pandemic, HIV-related stigma and stigma-enforcing stereotypes continue to serve as major health barriers to receiving adequate HIV prevention and treatment. While there continues to be a rise in research and advocacy, there is a need to study HIV stigma through a multigenerational lens that addresses the changing HIV/AIDS stigma in the post-apartheid era. Using qualitative methodology, this study aims to explore the generational differences in perceived HIV stigma between females in their 20s and above 50 years of age (as denoted by “50s+”) living in Cato Manor, South Africa. The study …

Up-03 Identifying The Determinants Of Pediatric Vaccine Uptake During The Covid-19 Pandemic, Colleen Phan, Brandon Mercardo, Justin Travis Ph.D., Ginny Webb Ph.D.

SC Upstate Research Symposium

COVID-19 has caused over a million deaths in the United States. Preventative measures such as masks, social distancing, and vaccination have been implemented to fight against the disease. Unfortunately, a large subset of Americans opposed these efforts.

SC DHEC reports that as of January 2023, only 53.9 % of eligible South Carolinians have been fully vaccinated against COVID-19. Previous studies have shown vaccine hesitancy is influenced largely by personal concerns about vaccine development, peer vaccination status, and general skepticism of immunization.

Hesitancy towards pediatric vaccination is particularly concerning because unvaccinated children can act as vessels to exponentially accelerate COVID-19 transmission. …

Small Molecule Compounds, Active Ingredients Of Tcm, As Novel Therapeutics For Eosinophilic Esophagitis, Anish Maskey

NYMC Student Theses and Dissertations

Eosinophilic Esophagitis (EoE), a chronic inflammatory condition of the esophagus, characterized by esophageal dysfunction and eosinophilic inflammation. Current treatments for EoE include dietary elimination and swallowed steroids. Recently, Dupixent was approved for the treatment of EoE, but it has side effects such as eye inflammation and eczema. Traditional Chinese Medicine (TCM) practice has been used to improve GI symptoms in EoE patients. Two key active ingredients of a TCM formula, 7,4’-Dihydroxyflavone (DHF) and Berberine (BBR), have shown remarkable results in treating EoE.

To understand the role of two active ingredients in EoE, different experimental models were used. First, a computational …

Time And Temperature Stability Of Tritrichomonas Foetus In Phosphate-Buffered Saline As Evaluated By A Reverse Transcription Real-Time Pcr Assay And Field Analysis, Duan S. Loy, Renata Spuri Gomes, Enakshy Dutta, Bruce W. Brodersen, John Dustin Loy

School of Veterinary and Biomedical Sciences: Faculty Publications

Tritrichomonas foetus (TF) is a significant reproductive pathogen of cattle, and sample collection, handling, transport, and testing are significant hurdles to surveillance programs. Recent methods have been developed that allow for the direct detection of TF using a reverse transcription real-time PCR (direct RT-qPCR) approach. To evaluate these methods, a comparative analysis was conducted to assess the technical performance of this assay with a commercially available real- time PCR (qPCR) assay. In addition, the evaluation of two types of collection media (PBS and TF transport tube) was conducted that evaluated sample stability from 0 to 3 days when stored at …

Role Of Nod2 Receptor In Immune Response To Staphylococcus Aureus, Precious Mckenzie, Aparna Palakodeti Ph.D

Research Days

Staphylococcus aureus, a gram-positive, commensal bacterium, causes several opportunistic diseases and infections in humans. Furthermore, some strains of S.aureus have developed resistance to antibiotics such as methicillin and pose a health risk. Pattern Recognition Receptors (PRRs) on host immune cells recognize specific components of S.aureus cell wall and mount an immune response against the bacteria. One such PRR is the Nuclear Oligomerization Domain 2 (NOD2) receptor which is present in the cytosol of host immune cells. NOD2 recognizes Muramyl-Dipeptide (MDP), a component of the peptidoglycan cell wall of several bacteria including S. aureus. The binding of MDP to NOD2 allows …

Impact Of Testosterone Use On The Vaginal Microbiota Of Transgender Men, Including Susceptibility To Bacterial Vaginosis: Study Protocol For A Prospective, Observational Study, Christina A. Muzny, Olivia T. Van Gerwen, Julia A. Schroeder, Emma Sophia Kay-Duncan, Krishmita Siwakoti, Kristal J. Aaron, Isaac C. Eastlund, Keonte J. Graves, Jacob H. Elnaggar, Ashutosh Tamhane, Dustin Long, Nicholas Van Wagoner, Evelyn Toh, Christopher M. Taylor

School of Graduate Studies Faculty Publications

Introduction The effect of testosterone (T) therapy on the vaginal microbiota of transgender men (TGM) is not well characterised, although one cross-sectional study comparing the vaginal microbiota of cisgender women to TGM on T≥1 year found that, in 71% of the TGM, the vaginal microbiota was less likely to be Lactobacillus-dominated and more likely to be enriched with >30 other bacterial species, many associated with bacterial vaginosis (BV). This prospective study aims to investigate changes in the composition of the vaginal microbiota over time in TGM who retain their natal genitalia (ie, vagina) and initiate T. In addition, we will …

Histone Deacetylase 8 Is A Novel Therapeutic Target For Mantle Cell Lymphoma And Preserves Natural Killer Cell Cytotoxic Function, January M. Watters

USF Tampa Graduate Theses and Dissertations

This study demonstrates for the first time that HDAC8 function is critical for MCL survival, and abrogating its activity in human primary NK cells does not interfere with NK IgG antibody directed ADCC therapies ex vivo. Human NK cells, isolated from healthy donors, are highly resistant to HDAC8 inhibitor treatment with PCI-34051. Even at the highest concentration, 20uM, no toxicity was observed. Conversely, MCL cell lines representative of the aggressive MCL subtype, classical MCL, were especially sensitive to PCI-34051, an HDAC8 selective inhibitor, treatment. Blocking HDAC8 activity and/or abrogating expression through shRNA silencing induced significant DNA damage, hyperacetylation of SMC3, …

Molecular Characterization Of The Antiviral Properties Of The Small Herc Family Of Proteins, Ermela Paparisto

Electronic Thesis and Dissertation Repository

Although viruses are obligate intracellular parasites, they have their own evolutionary trajectory, their genomes are in a constant battle to overcome the defenses of the host. This thesis investigates the role of the small HERC family of proteins in the battle against two deadly viruses: Human Immunodeficiency Virus -1 (HIV) and Zaire ebolavirus (EBOV). Although their discovery occurred decades ago, little knowledge is available about the small HERC family, their functions, and modes of interactions with other cellular proteins. In the first chapter, the structural evolution of the small HERC family and related functional changes that have occurred over time …

Rna Virus-Mediated Changes In Organismal Oxygen Consumption Rate In Young And Old Drosophila Melanogaster Males, Eli Hagedorn, Dean Bunnell, Beate Henschel, Daniel Smith Jr, Stephanie Dickinson, Andrew Brown, Maria De Luca, Ashley Turner, Stanislava Chtarbanova

Research, Publications & Creative Work

Aging is accompanied by increased susceptibility to infections including with viral pathogens resulting in higher morbidity and mortality among the elderly. Significant changes in host metabolism can take place following virus infection. Efficient immune responses are energetically costly, and viruses divert host molecular resources to promote their own replication. Virus-induced metabolic reprogramming could impact infection outcomes, however, how this is affected by aging and impacts organismal survival remains poorly understood. RNA virus infection of Drosophila melanogaster with Flock House virus (FHV) is an effective model to study antiviral responses with age, where older flies die faster than younger flies due …