Immunology and Infectious Disease Commons^™

A Monovalent Mt10-Cvb3 Vaccine Prevents Cvb4-Accelerated Type 1 Diabetes In Nod Mice, Mahima T. Rasquinha, Ninaad Lasrado, Meghna Sur, Kiruthiga Mone, Haowen Qiu, Jean-Jack Riethoven, Raymond A. Sobel, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Enteroviruses, which include Coxsackieviruses, are a common cause of virus infections in humans, and multiple serotypes of the group B Coxsackievirus (CVB) can induce similar diseases. No vaccines are currently available to prevent CVB infections because developing serotype-specific vaccines is not practical. Thus, developing a vaccine that induces protective immune responses for multiple serotypes is desired. In that direction, we created a live-attenuated CVB3 vaccine virus, designated mutant (Mt)10, that offers protection against myocarditis and pancreatitis induced by CVB3 and CVB4 in disease-susceptible A/J mice. Here, we report that the Mt10 vaccine protected against CVB4-triggered type 1 diabetes (T1D) in …

Taking Action: Turning Evolutionary Theory Into Preventive Policies, Orsolya Molnár, Marina Knickel, Christine Marizzi

MANTER: Journal of Parasite Biodiversity

The emerging infectious disease (EID) crisis has been challenging global health security for decades, dealing substantial damage to all socioeconomic landscapes. Control measures have failed to prevent or even mitigate damages from an accelerating wave of EIDs, leading to the emergence and devastation caused by the COVID-19 pandemic. In the wake of the pandemic, we must critically review our public health policies and approaches. Current health security measures are based on the evolutionary theorem of host-parasite coevolution, which falsely deems EIDs as rare and unpredictable. The DAMA protocol (Document, Assess, Monitor, Act) is nested in a novel evolutionary framework that …

The Stockholm Paradigm Explains The Dynamics Of Darwin’S Entangled Bank, Including Emerging Infectious Disease, Salvatore J. Agosta

MANTER: Journal of Parasite Biodiversity

Pathogens and their hosts are embedded within the larger biosphere, what Darwin called the “entangled bank.” Emerging infectious disease occurs when a parasite “switches” to a new host. Understanding the dynamics of emerging disease requires understanding the dynamics of host-switching, which requires a more general understanding of how the biosphere and its constituent members cope when conditions change. The Stockholm paradigm is an integrative evolutionary framework that describes how living systems cope with change by oscillating between exploiting and exploring the geographical and functional dimensions of their environments. It combines organismal capacity, ecological opportunity, and the repeated external perturbations to …

Characterizing The Function Of B Cells That Accumulate In The Inflamed Central Nervous System In Anti-Myelin Autoimmunity, Lika Chowdhury

Electronic Thesis and Dissertation Repository

While the role of autoimmune T cells has been extensively studied in anti-myelin

autoimmunity, little is known about the function of B cells in multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS). B cells form clusters with T cells in the meninges directly adjacent to demyelinating lesions. Previous studies have shown that disease progression is dependent on the depletion of specific populations of B cells, but it is not clear which contributes to pathology or how. The purpose of this thesis is to characterize the population of meningeal B cells to determine how they differ …

Anthelmintic Resistance In Sheep Across Ireland And The Uk: A Literature Review Of The In Vivo Versus In Vitro Methods, Megan Tumulty

SURE Journal: Science Undergraduate Research Experience Journal

Background: The animal welfare and production consequences of gastrointestinal nematode infections, namely Nematodirus battus, on sheep are compelling. The control of gastrointestinal infections has been heavily reliant on the administration of anthelmintics since their introduction into mainstream use in 1960. However, their frequent and often excessive use has resulted in anthelmintic resistance being reported extensively in several gastrointestinal nematode species. The prevalence of anthelmintic resistance as well as the increase in the number of cases of multiple-drug resistance in nematode populations now poses substantial hindrance on the viability of sheep production systems. However, despite the threat N. battus poses …

Knowing The Biosphere: Documentation, Specimens, Archives, And Names Reveal Environmental Change And Emerging Pathogens, Eric P. Hoberg, Valeria Trivellone, Joseph A. Cook, Jonathan L. Dunnum, Walter A. Boeger, Daniel R. Brooks, Salvatore J. Agosta, Jocelyn P. Colella

MANTER: Journal of Parasite Biodiversity

One Health programs and trajectories are now the apparent standard for exploring the occurrence and distribution of emerging pathogens and disease. By definition, One Health has been characterized as a broadly inclusive, collaborative, and transdisciplinary approach with connectivity across local to global scales, which integrates the medical and veterinary community to recognize health outcomes emerging at the environmental nexus for people, animals, plants, and their shared landscapes. One Health has been an incomplete model, conceptually and operationally, focused on reactive and response-based foundations, to limit the impact of emerging pathogens and emerging infectious diseases and, as such, lacks a powerful …

Surveillance Of Antimicrobial Resistance In Veterinary Medicine In The United States: Current Efforts, Challenges, And Opportunities, Juliana M. Ruzante, Beth Harris, Paul Plummer, Raissa R. Raineri, John Dustin Loy, Megan Jacob, Orhan Sahin, Amanda J. Kreuder

School of Veterinary and Biomedical Sciences: Faculty Publications

Antimicrobial resistance (AMR) is a global problem facing human, animal, plant, and environmental health by threatening our ability to effectively treat bacterial infections with antimicrobials. In the United States, robust surveillance efforts exist to collect, analyze, and disseminate AMR data in human health care settings. These tools enable the development of effective infection control methods, the detection of trends, and provide the evidence needed to guide stewardship efforts to reduce the potential for emergence and further spread of AMR. However, in veterinary medicine, there are currently no known equivalent tools. This paper reviews efforts to reduce the potential for emergence …

Crispr Technology As An Antiviral In Dsdna And Ssrna Viruses, Cathryn Mayes

Theses & Dissertations

The COVID-19 pandemic highlights the necessity of emergency response and pandemic preparedness, especially for emerging viral threats. Currently, virus-specific vaccines and antivirals are the primary tools to combat viral diseases; however, broad-spectrum antivirals that target more than one virus species could provide additional protection from emerging and re-emerging viral diseases (Andersen et al. 2020; Zhu et al. 2015; Hickman et al. 2022).

Clustered regulatory interspaced short palindromic repeat (CRISPR)-associated endonucleases have become recently utilized as potential antiviral strategies due to their high specificity, efficacy, and versatility (Najafi et al. 2022). While CRISPR-based antivirals have previously been used to target specific …

The Evolutionary Dynamics Of Infectious Diseases On An Unstable Planet: Insights From Modeling The Stockholm Paradigm, Angie T.C. Souza, Sabrina B.L. Araujo, Walter A. Boeger

MANTER: Journal of Parasite Biodiversity

Emerging infectious diseases (EIDs) are, besides a question of food safety and public health, an ecological and evolutionary issue. The recognition of this condition combined with the accumulation of evidence that pathogens are not specialists in their original hosts evidences the need for understanding how the dynamics of interaction between pathogens and hosts occurs. The Stockholm Paradigm (SP) provides the theoretical fundaments to understand the dynamics of diseases and design proactive measures to avoid the emergence and reemergence of infectious diseases. In this review, we revisit the models that evaluate several aspects of the proposed dynamics of the SP, including …

Tissue Resident Macrophages Drive Fibrosis During Pancreas Inflammatory Injury And Pancreatic Ductal Adenocarcinoma, John Baer

Arts & Sciences Electronic Theses and Dissertations

The immune system, and especially macrophages, are central in responding to infections, as well as providing a wide array of functions in other pathologies, especially in responding to inflammation. It is established that macrophages will accumulate within tissues during inflammation, many times secreting cytokines and chemokines central to the inflammatory response. This is particularly true during pancreatitis, or inflammation of the pancreas, where it has been shown that macrophages and monocytes accumulate in the pancreas to have various roles in further promoting inflammation. It is not well established, however, whether there are divergent roles for the distinct macrophage subsets that …

Nucleic Acid Extraction Of Human Immunodeficiency Virus From Municipal Wastewater, Fritz Vanderford, Hayley Baker, Ching-Lan Chang

Undergraduate Research Symposium Lightning Talks

In 2021, globally there were ~ 38.4 million people living with Human immunodeficiency virus (HIV), ~650,000 people died from acquired immunodeficiency syndrome (AIDS) related illnesses, ~1.5 million people acquired HIV. In the US, ~1.9 million people had HIV at the end of 2019, ~30,635 people were diagnosed with HIV in 2020.

Genotype Classification Of Moraxella Bovis Using Maldi-Tof Ms Profiles, Hannah G. Olson, John Dustin Loy, Michael L. Clawson, Emily L. Wynn, Matthew M. Hille

School of Veterinary and Biomedical Sciences: Faculty Publications

Moraxella bovis (M. bovis) is regarded as a causative agent of infectious bovine keratoconjunctivitis (IBK), the most common ocular disease of cattle. Recently, whole genome sequencing identified the presence of two distinct genotypes within M. bovis that differ in chromosome content, potential virulence factors, as well as prophage and plasmid profiles. It is unclear if the genotypes equally associate with IBK or if one is more likely to be isolated from IBK lesions. We utilized 39 strains of M. bovis that had previously undergone whole genome sequencing and genotype classification to determine the utility of matrix-assisted laser desorption/ionization …

Investigating The Involvement Of The Tick Vector In The Induction Of Alpha-Galactose Hypersensitivity (Alpha-Gal Syndrome, Red Meat Allergy) In The United States., Gary Crispell

Dissertations

Alpha-gal syndrome (AGS or sometimes called red meat allergy) is a result of the development of specific IgE antibodies to the oligosaccharide galactose-α-1,3-galactose (α-gal) after a person has had exposure to tick bites. This dissertation investigates four common tick species found in North America: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) for the presence of α-gal by utilizing a combination of immunoproteomic approaches and carbohydrate analysis techniques.

Anti-α-gal IgM antibodies (M86) were used in immunoblotting to detect …

Selection Pressure On Surface Exposed Virus Proteins, Sareh Bagherichimeh

Electronic Thesis and Dissertation Repository

Viral infection requires the interaction between virus surface-exposed (SE) proteins and host cell receptors. This can result in an “arms race” that is assumed to drive accelerated rates of evolution, and some well known examples of diversifying selection involve surface pro- teins (HIV-1 env, influenza hemagglutinin). We conducted a systematic analysis to determine whether this is truly a distinctive feature of SE virus proteins, in comparison to non-SE proteins encoded by the same genomes.

We obtained reference and all neighbour genomes of 52 human viruses from the NCBI Viral Genomes database. The coding sequences (CDS) of each genome extracted by …

Screening Anti-Pd-L2 Peptides As Antitumor Ligands Using Phage Display, Chien Tran Phuoc

Honors Projects

Cancer still remains one of the top leading causes of death in America. Recently, programmed cell death protein 1 (PD-1) blockades have been demonstrated to be highly effective against various types of cancer. By blocking PD-1 from binding with their ligands (PD-L1 and PD-L2), the “off” signal to the immune system is inhibited, hence reinvigorating the immune cells to kill tumor cells. To date, despite PD-L1 and PD-L2 both interacting with PD-1, research efforts have only been focused on developing anti-PD-L1 inhibitors. Therefore, the work of this honor project has focused on finding anti-PD-L2 peptides by phage display, with the …

Alternative Precautionary Measures Yielding Lower C. Diff Infection Rates In Healthcare Facilities, Matthew Kramer

Symposium of Student Scholars

Background: An international healthcare concern is the persistent spread of Clostridium difficile, a Gram-positive spore forming bacterium that is responsible for the most common hospital-acquired infection, amongst patients.

Objective: A systematic review was performed to summarize evidence that the interventions utilized in healthcare facilities which indicate a patient’s precautionary status are insufficient, outdated, and commonly lead to infection in neighboring patient rooms. Databases such as PubMed, NCBI, Google Scholar, and APHA’s Medical Care were searched, covering the period from 2017-2022. Studies were included if their focus concentrated on C. diff and the precautionary measures taken by employees at healthcare …

Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal

Electronic Theses and Dissertations

Human Immunodeficiency Virus (HIV) infection initiates major metabolic and cell- survival complications. Anti-retroviral therapy (ART) is the current approach to suppress active HIV replication to a level of undetected viral load, but it is not a curative approach. Newer and sophisticated gene editing technologies could indeed be a potent antiviral therapy to achieve a clinical sterilization/cure of HIV infection. Chronic HIV patients, even under a successful ART regimen, exhibit a low-grade inflammation, immune senescence, premature aging, telomeric DNA attrition, T cell apoptosis, and cellular homeostasis. In this dissertation, we investigated CD4 T cell homeostasis, degree of T cell apoptosis, an …

A Novel Transmembrane Ligand Inhibits T Cell Receptor Activation, Yujie Ye

Doctoral Dissertations

T lymphocytes (T cells) play essential roles in the adaptive immune system. Each mature T cell expresses one type of functional T cell receptor (TCR). The TCR recognizes antigens bound to the major histocompatibility complex (MHC) in antigen presenting cells. The resulting stimulation signal crosses the transmembrane domain of TCR and initiates downstream signaling cascades. The human immune system relies on TCRs to recognize a variety of pathogens. Normally, TCR can distinguish the self-antigens from pathogenic antigens. However, dysfunction or aberrant expression of TCRs causes different inflammatory and autoimmune diseases, which afflict millions of people annually (Chapter I). Current treatments …

Optimization Of Clostridium Septicum Antigen Production And Evaluation Of Vaccine Administration Parameters For A Candidate Bacterin-Toxoid To Prevent Dermatitis In Commercial Turkeys, Aaron Forga

Graduate Theses and Dissertations

The objective of this thesis was to optimize the hemolytic activity of two isolates of Clostridium septicum to evaluate if hemolytic titer of C. septicum antigen at time of formalin inactivation corresponded to increased serum antibody titer to the C. septicum alpha-toxin of turkeys immunized with an experimental formalin inactivated bacterin-toxoid vaccine. Chapter 1 provides a brief overview of the thesis. Chapter 2 consists of a literature review focused on clostridial dermatitis, specifically C. septicum-associated dermatitis (cellulitis) that affects commercial turkeys. Chapter 3 outlines our attempts to optimize an experimental autogenous bacterin-toxoid vaccine as a potential strategy to mitigate clostridial …

T-Cell Antigen Receptors In Multiple Sclerosis, Lisa Lanée Keyes Jones

Biomedical Sciences Theses & Dissertations

Multiple Sclerosis (MS) is T-cell mediated autoimmune disease characterized by inflammation, demyelination, and degeneration of axons in the brain and spinal cord. A T cell-mediated immune response in MS is directed against myelin components and possibly other antigens in genetically susceptible individuals and is triggered by a viral infection. The T-cell antigen receptor (TCR) on T cells is responsible for antigen recognition and determines specificity. Our overall hypothesis is to determine whether clonally expanded T cells in patients with MS recognize viral or self-antigens and to determine whether molecular mimicry is involved in the development of the disease. To study …