Immunology and Infectious Disease Commons^™

The Presence Of Tetracycline-Resistant Bacteria In A Kean University Campus Soil Sample, Esther Blankson, Jessica Kobilas, Gianna Medeiros

Kean Quest

The spread of antimicrobial resistance (AMR) in the environment is a worldwide problem that threatens human health. Bacteria are becoming increasingly resistant to antibiotics as the consumption of antibiotics grows. In particular, soil can be contaminated with bacteria that are resistant to antibiotics. As of today, there is no surveillance system that tracks the spread of antibiotic-resistant bacteria, however, Tufts University aims to change this by implementing the Prevalence of Antibiotic Resistance in the Environment (PARE) project. The course-based PARE project consists of research students sampling soil in diverse locations and reporting the prevalence of antibiotic-resistant bacteria. The purpose of …

The Role Of Community In Immunity Against Sars-Cov-2, Jessica Kobilas

Kean Quest

This literature review investigated the roles genes activated by social interactions had in helping to build immunity against COVID-19. Past studies have shown that individuals who are more socially connected are less likely to become ill due to social interactions strengthening the immune system through optimal exposure to bacteria and viruses in the environment. The IL-6 and TLR4 genes that are activated through social interactions and associated with cytokines have been analyzed in cases of various viral infections. Cytokines play a role in inflammation and have both pro-inflammatory and anti-inflammatory responses to infections and viruses. The results suggest that the …

Cancer-Specific Perturbations To Arginine Metabolism Blunt Replication And Performance Of Oncolytic Myxoma Virus, Parker Dryja

MUSC Theses and Dissertations

Oncolytic virotherapy (OV) is a class of immunotherapy for treatment of malignancy. Using viruses that exhibit natural coincidental tropisms for cancer, or others that have been engineered to the same effect, intentional infection of lesions leads to two therapeutically beneficial effects: (1) direct destruction of the infected tumor through virally-mediated cell lysis, and (2) recruitment of an otherwise blunted or absent anti-cancer immune response to affect both local and disseminated disease. A surfeit of cancer-specific changes are accumulated during progression from first genetic insult to clinical detection, presenting a dramatically altered underlying biology of cell and tissue. The viruses employed …

The Abscopal Effect In Patients With Cancer Receiving Immunotherapy, Blessie Elizabeth Nelson, Jacob J Adashek, Steven H Lin, Vivek Subbiah

Faculty, Staff and Student Publications

Interest in the abscopal effect has been rekindled over the past decade with the advent of immunotherapy. Although purportedly elusive, this phenomenon is being increasingly reported. Venturing further using a multimodality approach with an array of systemic agents and unconventional modalities is direly needed. In this perspective, we describe the fundamentals of abscopal responses (ARs), explore combinations with systemic therapies that hold promise in eliciting ARs, and reconnoiter unconventional modalities that may induce ARs. Finally, we scrutinize prospective agents and modalities that exhibit preclinical ability to elicit ARs and discuss prognostic biomarkers, their limitations, and pathways of abscopal resistance for …

Serinc5 Restricts Hiv Membrane Fusion By Altering Lipid Order And Heterogeneity In The Viral Membrane, Amanda E Ward, Daria Sokovikova, Melvin Neal Waxham, Frederick A Heberle, Ilya Levental, Kandice R Levental, Volker Kiessling, Judith M White, Lukas K Tamm

Faculty, Staff and Student Publications

The host restriction factor, Serinc5, incorporates into budding HIV particles and inhibits their infection by an incompletely understood mechanism. We have previously reported that Serinc5 but not its paralogue, Serinc2, blocks HIV cell entry by membrane fusion, specifically by inhibiting fusion pore formation and dilation. A body of work suggests that Serinc5 may alter the conformation and clustering of the HIV fusion protein, Env. To contribute an additional perspective to the developing model of Serinc5 restriction, we assessed Serinc2 and Serinc5's effects on HIV pseudoviral membranes. By measuring pseudoviral membrane thickness via cryo-electron microscopy and order via the fluorescent dye, …

Assessment Of Anti-Hiv-1 Guide Rna Efficacy In Cells Containing The Viral Target Sequence, Corresponding Grna, And Crispr/Cas9., Alexander G Allen, Cheng-Han Chung, Stephen D. Worrell, Glad Nwaozo, Rebekah Madrid, Anthony R. Mele, Will Dampier, Michael R. Nonnemacher, Brian Wigdahl

Kimmel Cancer Center Faculty Papers

The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 gene editing system has been shown to be effective at inhibiting human immunodeficiency virus type 1 (HIV-1). Studies have not consistently used a trackable dual reporter system to determine what cells received the Cas9/gRNA to determine the overall knockdown of HIV. Some studies have used stably transduced cells under drug selection to accomplish this goal. Here a two-color system was used that allows tracking of viral protein expression and which cells received the CRISPR/Cas9 system. These experiments ensured that each gRNA used was a perfect match to the intended target to remove …

Treating Yellow Fever Virus With The Antiviral Bdaa And Effects On The Immune Response In An Animal Model, Abbie Weight

Student Research Symposium

Yellow fever virus (YFV) is a mosquito-borne virus with a considerable disease burden in South America and Africa and no approved antivirals. BDAA is an experimental antiviral for YFV which inhibits the viral protein NS4B and is effective against YFV in cell culture and a hamster model. Along with directly inhibiting virus replication, treating YFV-infected cells with BDAA increases the detection and response to foreign RNA by the host cell by releasing YFV replication intermediates into the cytoplasm. While this has been shown in cell culture, it is important to understand if this immune effect is relevant to BDAA’s efficacy …

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 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 …

Does Stress Physiology Mediate Disease Resistance In The Arizona Tiger Salamander (Ambystoma Mavortium Nebulosum)?, Megan Zerger

2023 Midwest Ecology & Evolution Conference

Amphibian biodiversity has greatly diminished in recent years due to disease. Panzootic pathogenic fungi Batrachochytrium dendrobatidis (Bd) causes the deadly disease chytridiomycosis (chytrid), a primary driver of catastrophic global amphibian declines and extinctions. The pathogenesis of chytrid is still unclear, as certain species and individuals within a species are differentially affected. Susceptibility and mortality of Bd are influenced by prolonged chronic stress. Prolonged glucocorticoid activity deleteriously affects many of the same physiological processes as Bd infections, and corticosterone is the primary glucocorticoid released by amphibians in response to stress. Thus, the objective of our study is to assess …

Spatiotemporal Patterns Of Ticks And Tick-Borne Disease Dynamics At Neon Sites Across A Sub-Continental Scale., Ana Sofia Rivera

2023 Midwest Ecology & Evolution Conference

At local scales, dynamics of ticks and tick-borne diseases such as Lyme disease are driven by resource pulses, such as mast seeding in forest trees, that creates increases in tick hosts. Tick-borne diseases in humans have nearly doubled between 1940 and 2004 and understanding the dynamics of infectious diseases has long been of interest for ecologists. The family Ixodidae is the most capable of transmitting pathogens to humans and tick-borne diseases are the most common vector of illness in the United States. The objective of this research is to characterize the spatiotemporal dynamics of ticks and tick-borne diseases, which may …

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 …

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. …

Resources For Preparing And Using Antibiograms In Hospital Settings, Fred Tenover, Dana Tawa, Stephanie Mitchell, Isabella A. Tickler, John Stelling, Janet Hindler, Debra A. Goff, Dan Diekema

Training Materials on Antimicrobial Resistance

This is a guide to resources that are available to assist laboratories with the preparation and dissemination of their antimicrobial susceptibility testing data in a format known as an "antibiogram" as an aid to antimicrobial stewardship activities in their hospital. There are three color-coded pathways in the slide deck: Pathway A for laboratories with no experience with antibiograms; Pathway B for laboratories with some experience that want to improve and expand the use of their antibiograms; and Pathway C for experienced laboratories that want to share their data with external surveillance systems.

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 …

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 …

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 …

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

Dissertations and 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 …

Letter To The Editor: Quality Criteria For Computational Models Predicting Individual Outcomes In Car-T Cell Therapy, Anna M Mc Laughlin, Cassian Yee

Faculty, Staff and Student Publications

No abstract provided.

A Non-Antibiotic-Disrupted Gut Microbiome Is Associated With Clinical Responses To Cd19-Car-T Cell Cancer Immunotherapy, Christoph K Stein-Thoeringer, Neeraj Y Saini, Eli Zamir, Viktoria Blumenberg, Maria-Luisa Schubert, Uria Mor, Matthias A Fante, Sabine Schmidt, Eiko Hayase, Tomo Hayase, Roman Rohrbach, Chia-Chi Chang, Lauren Mcdaniel, Ivonne Flores, Rogier Gaiser, Matthias Edinger, Daniel Wolff, Martin Heidenreich, Paolo Strati, Ranjit Nair, Dai Chihara, Luis E Fayad, Sairah Ahmed, Swaminathan P Iyer, Raphael E Steiner, Preetesh Jain, Loretta J Nastoupil, Jason Westin, Reetakshi Arora, Michael L Wang, Joel Turner, Meghan Menges, Melanie Hidalgo-Vargas, Kayla Reid, Peter Dreger, Anita Schmitt, Carsten Müller-Tidow, Frederick L Locke, Marco L Davila, Richard E Champlin, Christopher R Flowers, Elizabeth J Shpall, Hendrik Poeck, Sattva S Neelapu, Michael Schmitt, Marion Subklewe, Michael D Jain, Robert R Jenq, Eran Elinav

Faculty, Staff and Student Publications

Increasing evidence suggests that the gut microbiome may modulate the efficacy of cancer immunotherapy. In a B cell lymphoma patient cohort from five centers in Germany and the United States (Germany, n = 66; United States, n = 106; total, n = 172), we demonstrate that wide-spectrum antibiotics treatment ('high-risk antibiotics') prior to CD19-targeted chimeric antigen receptor (CAR)-T cell therapy is associated with adverse outcomes, but this effect is likely to be confounded by an increased pretreatment tumor burden and systemic inflammation in patients pretreated with high-risk antibiotics. To resolve this confounding effect and gain insights into antibiotics-masked microbiome signals …

Clinical Outcomes Of Immune Checkpoint Inhibitor Diabetes Mellitus At A Comprehensive Cancer Center, Rebecca Jeun, Priyanka C Iyer, Conor Best, Victor Lavis, Jeena M Varghese, Sireesha Yedururi, Veronica Brady, Isabella C Glitza Oliva, Ramona Dadu, Denai R Milton, Kristy Brock, Sonali Thosani

Faculty, Staff and Student Publications

Introduction: Immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) is a rare adverse event. In this study, we characterize clinical outcomes of patients with ICI-DM and evaluate survival impact of this complication on melanoma patients.

Research design & methods: We conducted a retrospective review of 76 patients diagnosed with ICI-DM from April 2014 to December 2020.

Results: 68% of patients presented in diabetic ketoacidosis, 16% had readmissions for hyperglycemia, and hypoglycemia occurred in 70% of patients after diagnosis. Development of ICI-DM did not impact overall survival or progression-free survival in melanoma patients.

Conclusion: Development of ICI-DM is associated with long-term insulin dependence …

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 …

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 …

Partial Characterization Of Plasmodium Falciparum Genes Implicated In Altered Artemisinin Stress Response, Caroline F. Simmons

USF Tampa Graduate Theses and Dissertations

Malaria is a parasitic illness caused by the Plasmodium spp., with an estimated 247 million malaria cases reported in 2021 across 84 endemic countries. Treatment of the deadliest malaria parasite, P. falciparum, relies on artemisinin combination therapies (ACTs). However, while ACTs have greatly decreased malaria mortality, this progress is threatened due to artemisinin (ART) partial resistance and ACT failure in Southeast Asia and Sub-Saharan Africa. SNPs to the Kelch13 (K13) gene are a well-characterized marker for ART resistance. However, increasing evidence that resistance to ART mediated by genes not related to K13 SNPs prompts the need to characterize other novel …

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 …