Immunology and Infectious Disease Commons^™

Fibrinogen-Like Protein 2: Its Biological Function Across Cell Types And The Potential To Serve As An Immunotherapy Target For Brain Tumors, Sheng Zhang, Ganesh Rao, Amy Heimberger, Shulin Li

Faculty, Staff and Student Publications

Brain tumors are among the 10 leading causes of cancer-related death and present unique treatment challenges due to their critical location, genetic heterogeneity, and the blood-brain barrier. Recent advances in targeted immunotherapy and immune checkpoint blocking therapy provide alternative therapeutic strategies for brain tumors. Fibrinogen-like protein 2 (FGL2), which induces transformation from low-grade glioma to high-grade glioblastoma, is a type II membrane protein that is highly expressed in both host immune cells and tumor cells. Studies have uncovered multiple forms of FGL2 proteins with a broad range of roles in inducing immune tolerance and avoiding immune surveillance in tumor cells. …

The Immune Modulation On Innate Immunity, From Pathogen Recognition To Fungal Clearance., Ko-Wei Liu

Dartmouth College Ph.D Dissertations

The human lung is not sterile but a complex environment with various microorganisms. Besides commensals in the lung, hundreds to thousands of individual microbiomes enter the lung every day but without causing the symptom. Host innate immunity plays an important role in maintaining homeostasis of the lung environment and as the first defense line against pathogens. Aspergillus fumigatus (A. fumigatus) is a saprophytic filamentous fungus that can cause human disease in immune compromised patients. However, with functional innate immunity, immune cells can quickly recognize pathogen associated molecular patterns (PAMPs) from A. fumigatus through pattern recognition receptors (PRRs). The activation of …

Autonomic Function Recovery And Physical Activity Levels In Post-Covid-19 Young Adults After Immunization: An Observational Follow-Up Case-Control Study, Ana Paula Coelho Figueira Freire, Shaan Amin, Fabio Santos Lira, Ana Elisa Von Ah Morano, Telmo Pereira, Manuel-João Coelho-E-Silva, Armando Caseiro, Diego Giulliano Destro Christofaro, Vanessa Ribeiro Dos Santos, Osmar Marchioto Júnior, Ricardo Aurino Pinho, Bruna Spolador De Alencar Silva

All Faculty Scholarship for the College of Education and Professional Studies

Coronavirus disease 2019 (COVID-19) has detrimental multi-system consequences. Symptoms may appear during the acute phase of infection, but the literature on long-term recovery of young adults after mild to moderate infection is lacking. Heart rate variability (HRV) allows for the observation of autonomic nervous system (ANS) modulation post-SARS-CoV-2 infection. Since physical activity (PA) can help improve ANS modulation, investigating factors that can influence HRV outcomes after COVID-19 is essential to advancements in care and intervention strategies. Clinicians may use this research to aid in the development of non-medication interventions. At baseline, 18 control (CT) and 20 post-COVID-19 (PCOV) participants were …

Displaying And Delivering Viral Membrane Antigens Via Ww Domain–Activated Extracellular Vesicles, Sengjin Choi, Zhiping Yang, Qiyu Wang, Zhi Qiao, Maoyun Sun, Joshua Wiggins, Shi-Hua Xiang, Quan Lu

School of Veterinary and Biomedical Sciences: Faculty Publications

Membrane proteins expressed on the surface of enveloped viruses are conformational antigens readily recognized by B cells of the immune system. An effective vaccine would require the synthesis and delivery of these native conformational antigens in lipid membranes that preserve specific epitope structures. We have created an extracellular vesicle–based technology that allows viral membrane antigens to be selectively recruited onto the surface of WW domain–activated extracellular vesicles (WAEVs). Budding of WAEVs requires secretory carrier-associated membrane protein 3, which through its proline-proline-alanine-tyrosine motif interacts with WW domains to recruit fused viral membrane antigens onto WAEVs. Immunization with influenza and HIV viral …

Vaccines Against Group B Coxsackieviruses And Their Importance, Kiruthiga Mone, Ninaad Lasrado, Meghna Sur, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

The group B coxsackieviruses (CVBs) exist in six serotypes (CVB1 to CVB6). Disease associations have been reported for most serotypes, and multiple serotypes can cause similar diseases. For example, CVB1, CVB3, and CVB5 are generally implicated in the causation of myocarditis, whereas CVB1 and CVB4 could accelerate the development of type 1 diabetes (T1D). Yet, no vaccines against these viruses are currently available. In this review, we have analyzed the attributes of experimentally tested vaccines and discussed their merits and demerits or limitations, as well as their impact in preventing infections, most importantly myocarditis and T1D.

The Impacts Of Immune Challenges On Fish Behavior And Physiology, Teisha King

LSU Doctoral Dissertations

For species living in dominance hierarchies, social rank dictates access to resources and often contributes to reproductive success. To ensure survival, individuals constantly evaluate trade- offs between crucial biological systems, like the reproductive and immune systems, depending on their social rank and physiological state. Little is known about how social species balance interactions between immune system function, fluctuations in social status and reproductive fitness, and the performance of behaviors necessary for maintaining social status when sick, particularly in fishes, the largest and most diverse group of vertebrates. My dissertation research uses a whole animal approach to examine how physiological profiles …

Personalized Matched Targeted Therapy In Advanced Pancreatic Cancer: A Pilot Cohort Analysis, Justin Shaya, Shumei Kato, Jacob J. Adashek, Hitendra Patel, Paul T. Fanta, Gregory P. Botta, Jason K. Sicklick, Razelle Kurzrock

School of Veterinary and Biomedical Sciences: Faculty Publications

Despite progress, 2-year pancreatic cancer survival remains dismal. We evaluated a biomarker-driven, combination/N-of-one strategy in 18 patients (advanced/metastatic pancreatic cancer) (from Molecular Tumor Board). Targeted agents administered/ patient = 2.5 (median) (range, 1–4); first-line therapy (N = 5); second line, (N = 13). Comparing patients (high versus low degrees of matching) (matching score ≥50% versus <50%; reflecting number of alterations matched to targeted agents divided by number of pathogenic alterations), survival was significantly longer (hazard ratio [HR] 0.24 (95% confidence interval [CI], 0.078–0.76, P = 0.016); clinical benefit rates (CBR) (stable disease ≥6 months/partial/complete response) trended higher (45.5 vs 0.0%, P = 0.10); progression-free survival, HR, 95% CI, 0.36 (0.12–1.10) (p = 0.075). First versus ≥2nd-line therapy had higher CBRs (80.0 vs 7.7%, P = …

Utilizing Neoantigen-Specific Cd4* T Cells And Immune Checkpoint Modulation To Advance Adoptive Cell Therapy With Tumor-Infiltrating Lymphocytes For Metastatic Melanoma Patients, Maclean Scott Hall

USF Tampa Graduate Theses and Dissertations

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is a promising immunotherapeutic approach for patients with advanced solid tumors. Metastatic melanoma is a tumor type amenable to immunotherapy in part due to the presence of antigen-specific TIL. These T cells can be activated and expanded for ACT, which has resulted in relatively high rates of clinical responses. While numerous advances have been made, the inclusion of neoantigen-specific CD4+ T cells within TIL infusion products remains underexplored and therefore offers a significant opportunity for progress. Similarly, immune checkpoint inhibitors, specifically PD-1 blocking antibodies, augment antitumor immunity and may improve the outcomes …

Antibody-Dependent Enhancement Activity Of A Plant-Made Vaccine Against West Nile Virus, Amber M. Paul, Haiyan Sun, Dhiraj Acharya, Huafang Lai, Junyun He, Fengwei Bai, Qiang Chen

Publications

West Nile virus (WNV) causes annual outbreaks globally and is the leading cause of mosquito-borne disease in Unite States. In the absence of licensed therapeutics, there is an urgent need to develop effective and safe human vaccines against WNV. One of the major safety concerns for WNV vaccine development is the risk of increasing infection by related flaviviruses in vaccinated subjects via antibody-dependent enhancement of infection (ADE). Herein, we report the development of a plant-based vaccine candidate that provides protective immunity against a lethal WNV challenge mice, while minimizes the risk of ADE for infection by Zika (ZIKV) and dengue …

Antibody Duration After Infection From Sars-Cov-2 In The Texas Coronavirus Antibody Response Survey, Michael D Swartz, Stacia M Desantis, Ashraf Yaseen, Frances A Brito, Melissa A Valerio-Shewmaker, Sarah E Messiah, Luis G Leon-Novelo, Harold W Kohl, Cesar L Pinzon-Gomez, Tianyao Hao, Shiming Zhang, Yashar Talebi, Joy Yoo, Jessica R Ross, Michael O Gonzalez, Leqing Wu, Steven H Kelder, Mark Silberman, Samantha Tuzo, Stephen J Pont, Jennifer A Shuford, David Lakey, Eric Boerwinkle

Faculty, Staff and Student Publications

Understanding the duration of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that causes COVID-19 is important to controlling the current pandemic. Participants from the Texas Coronavirus Antibody Response Survey (Texas CARES) with at least 1 nucleocapsid protein antibody test were selected for a longitudinal analysis of antibody duration. A linear mixed model was fit to data from participants (n = 4553) with 1 to 3 antibody tests over 11 months (1 October 2020 to 16 September 2021), and models fit showed that expected antibody response after COVID-19 infection robustly increases for 100 days postinfection, and predicts …

The Future Of Pandemics: Land Use Controls As Means Of Preventing Zoonotic Disease, Bailey Andree

Pace International Law Review

Zoonotic diseases are increasing in frequency as climate change worsens around the world, with the recent COVID-19 pandemic highlighting the inadequate mechanisms in place to counteract disease spread. This article reviews various zoonotic diseases and their patterns of spread, highlighting land use change as the key driver of disease to demonstrate the need for legal intervention. International land use law is a little-developed subsect of environmental law that holds the key to combating this disease spread, and this article proposes solutions through this legal lens. Land use techniques which may be used to combat disease spread include conservation laws, setback …

Phase 1a Clinical Study For Q-Griffithsin Intranasal Spray For Prevention Of Coronavirus, Megan Bezold, Kenneth Palmer, Nobuyuki Matoba, Elizabeth Cash

Posters-at-the-Capitol

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible virus that causes acute respiratory disease with possible long-term complications, known as coronavirus disease 2019 (COVID-19). Griffithsin (GRFT; including the oxidation-resistant variant Q-GRFT used in this study) is an algal carbohydrate-binding protein exhibiting antiviral effects against many enveloped viruses, including all major variants of SARS- CoV-2 reported to date. Q-GRFT has been recombinantly manufactured in Nicotiana benthamiana plants, thoroughly purified, and formulated as an intranasal spray designed to be developed as a non-vaccine broad-spectrum prophylactic product for acute use. This is the first-in-human, randomized, double-blind, placebo-controlled study. The …

A Dynamical System Model Of Dengue Transmission For Rio De Janeiro, Brazil, Gregory Schmidt, Benjamin Whipple, Vinodh Chellamuthu, Xiaoxia Xie

Spora: A Journal of Biomathematics

The dengue virus is a serious concern in many parts of the world, including Brazil. As data indicates, a prominent vector for dengue is the mosquito Aedes aegypti. By using the dengue incidence records from the Brazilian SINAN database, we estimate the population of A. aegypti within the city of Rio de Janeiro. Using historical climate data for Rio de Janeiro and the computed population estimates, we extend an existing model for the population dynamics of mosquitoes to incorporate precipitation in aquatic stages of development for A. aegypti.

Molecular Regulation Of The Salicylic Acid Hormone Pathway In Plants Under Changing Environmental Conditions, Christina A. M. Rossi, Eric J. R. Marchetta, Jong Hum Kim, Christian Castroverde

Biology Faculty Publications

Salicylic acid (SA) is a central plant hormone mediating immunity, growth, and development. Recently, studies have highlighted the sensitivity of the SA pathway to changing climatic factors and the plant microbiome. Here we summarize organizing principles and themes in the regulation of SA biosynthesis, signaling, and metabolism by changing abiotic/biotic environments, focusing on molecular nodes governing SA pathway vulnerability or resilience. We especially highlight advances in the thermosensitive mechanisms underpinning SA-mediated immunity, including differential regulation of key transcription factors (e.g., CAMTAs, CBP60g, SARD1, bHLH059), selective protein–protein interactions of the SA receptor NPR1, and dynamic phase separation of the recently identified …

A Novel Therapeutic Approach To Regulate Carex8 Protein Expression Through E6-Conjugated Cell Penetrating Peptides, Jared D. Compaleo

Browse all Theses and Dissertations

Adenovirus is a human pathogen that causes cold like symptoms in healthy individuals, which could be lethal in pediatrics and the immunocompromised. In polarized epithelia, adenovirus uses the eight-exon isoform of the Coxsackievirus and Adenovirus Receptor (CAREx8) on the apical surface, to facilitate infection. CAREx8 protein expression level is regulated by the scaffolding protein MAGI-1, using two of its PSD95/Dlg-1/ZO-1 (PDZ) domains: PDZ2 and PDZ4. We previously showed that CAREx8 is degraded after interaction with PDZ4 and rescued following interaction with PDZ2. We then developed a PDZ2 binding decoy molecule (E6) that blocks the interaction between CAREx8 and PDZ2, which …

The Role Of Schwann Cells In Nerve Injury: Forskolin-Mediated Camp Activation Upregulates Tnfα Expression Despite Nf-Κb Downregulation In Lps-Treated Schwann Cells, Caitlyn E. Henry, Angela L. Asirvatham Ph.D.

Student Research Poster Presentations 2023

Although Schwann cells are known to play a role in axonal regeneration following nerve injury and inflammation, the exact mechanism is unknown. This study explores two potential mechanisms: the NF-κB and cAMP pathways. The NF-κB pathway produces cytokines, such as TNFα, to regulate inflammation, whereas the cAMP pathway is anti-inflammatory and regulates Schwann cell proliferation via AKAP95 and cyclin D3. Although it is well-known that NF-κB and cAMP are involved in inflammation, not much is known regarding the effects of forskolin-mediated cAMP activation on LPS-mediated NF-κB activation in Schwann cells. In this study, RT4-D6P2T immortalized rat Schwann cells were treated …

Fair Domestic Allocation Of Monkeypox Virus Countermeasures, Govind C. Persad, R. J. Leland, Trygve Ottersen, Henry S. Richardson, Carla Saenz, G. Owen Schaefer, Ezekiel J. Emanuel

Sturm College of Law: Faculty Scholarship

Countermeasures for mpox (formerly known as monkeypox), primarily vaccines, have been in limited supply in many countries during outbreaks. Equitable allocation of scarce resources during public health emergencies is a complex challenge. Identifying the objectives and core values for the allocation of mpox countermeasures, using those values to provide guidance for priority groups and prioritisation tiers, and optimising allocation implementation are important. The fundamental values for the allocation of mpox countermeasures are: preventing death and illness; reducing the association between death or illness and unjust disparities; prioritising those who prevent harm or mitigate disparities; recognising contributions to combating an outbreak; …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

UROP Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

Understanding Inflammation, Immunity, And Infection, Jeff Vasiloff, Md, Mph

OHIO Open Faculty Textbooks

Inflammation, immunity, and infection explained by Jeffrey Vasiloff, MD, MPH, Associate Clinical Professor, PA Program; Adjunct Professor, PT Program, College of Health Sciences and Professions, Ohio University Dublin Medical Campus; Physician Consultant: Ohio Association of Physician Assistants; Physician Volunteer: Franklin County & Columbus Medical Reserve Corps; Board Certification: Internal Medicine & Diabetes and Endocrinology.

Tissue And Sex-Dependent Regulation Of Innate Immunity And Rna Editing In Mice, Kelsey R. Kendrick

Graduate Theses/Dissertations

Inflammation occurs as a result of insult or infection within the body. Individual cells respond to inflammation by upregulating genes that help mediate the immune response, such as ADAR1. ADAR1 helps regulate the immune response but also catalyzes a process called RNA editing. RNA editing alters the sequence of select mRNAs to alter the encoded proteins. The result is altered function of the encoded protein, which is often beneficial for the cell. Our goal was to determine how inflammation affects the function of ADAR1. Since we know that the effects of inflammation vary between different organs and sexes, we examined …

Sex-Dependent Effects Of Induced Acute Inflammation On Glucose Homeostasis And Rna Editing Enzymes, Christian A. Rivas

Graduate Theses/Dissertations

The first line of defense against bodily insults, like pathogen invasion, is the innate immune system. Innate immunity sets in motion countless cascades that result in inflammation. Inflammation simultaneously affects multiple biological processes like metabolism and gene expression. Males and females react differently to inflammation. To understand both molecular and physiological sex differences in inflammation, we examined how inflammation affects gene expression and glucose metabolism. Adenosine deaminase acting on RNA (ADAR1) is upregulated by inflammation and catalyzes RNA editing, a process where nucleotides encoded by the genome are modified. ADAR1 also controls the innate immune reaction by decreasing activity of …

Influence Of Cell Cycle On Aim2 Inflammasome Activation, Ashok Kumar Dubey

Graduate Theses/Dissertations

A cell cycle's progression has a significant role in the development of a disease. All the signaling pathways and inflammatory reactions are maintained in a healthy mode if cell cycle checkpoints are precisely regulated and kept in homeostasis. AIM2 inflammasome is a cytoplasmic double-stranded DNA sensor. Upon activation, it elicits an inflammatory reaction with the release of pro-inflammatory cytokines such as IL-1β and IL-18 and they are cleaved by the proteases, Caspase-1 from their inactive form. Also, the AIM2 inflammasome helps in regulating cell division and inhibits cell proliferation; thus, leading to a cell death called pyroptosis. Here, I examined …

Immune Checkpoint Inhibitors: Friend Or Foe, Antonio Cordova, Md, Jesse Powell, Md, Whitney Elg-Salsman, Md, Caroline Mcculley, Md

Poster Presentations

No abstract provided.

Investigation Of Bacterial Infection And Immunity In The Body Louse, Lauren Mae Kress

Dissertations and Theses

The human body louse (Pediculus humanus humanus) is a host-specific hematophagous ectoparasite that frequently infests populations experiencing a breakdown of hygienic conditions. Body lice are vectors for several bacterial human pathogens, including Borrelia recurrentis (relapsing fever), Rickettsia prowazekii (epidemic typhus) and Bartonella quintana (trench fever) (Badiaga & Brouqui 2012, Amanzougaghene et al. 2020). Today, louse-borne relapsing fever and epidemic typhus are largely geographically restricted to small foci in East Africa. However, B. quintana is a re-emerging and underappreciated pathogen throughout the globe, especially in urban environments (Mai 2022). Transmission of B. quintana is known to occur via inoculation of infectious …

Writing New Normals: A Study Of American Pandemic Fiction In The Wake Of Covid-19, Riley E. Droppleman

Gaines Fellow Senior Theses

The purpose of this thesis is to explore the aspects of pandemic fiction that extend beyond the illness itself. In this thesis, I show that while the disease that spreads is a large focus of pandemic fiction, the truths that spring from these novels reveal larger societal issues, such as class hierarchies, racial inequalities, and failings of the government to fight the pandemic. In fact, pandemics act as catalysts for the uncovering of these societal ills, and the authors of pandemic fictions bring these greater faults of society to the forefront of their novels. I analyze three novels from the …

Relative Adrenal Insufficiency Is A Risk Factor And Endotype Of Sepsis - A Proof-Of- Concept Study To Support A Precision Medicine Approach To Guide Glucocorticoid Therapy For Sepsis, Chia-Hua Wu, Ling Guo, Dan Hao, Qian Wang, Xiang Ye, Misa Ito, Bin Huang, Chieko Mineo, Philip W. Shaul, Xiang-An Li

Saha Cardiovascular Research Center Faculty Publications

Introduction: 25-60% of septic patients experience relative adrenal insufficiency (RAI) and glucocorticoid (GC) is frequently used in septic patients. However, the efficacy of GC therapy and whether GC therapy should be based on the status of RAI are highly controversial. Our poor understanding about the pathogenesis of RAI and a lack of RAI animal model present significant barriers to address these critical issues.

Methods: Scavenger receptor BI (SR-BI) regulates stress-induced GC (iGC) production in response to stress. We generated SF1CreSR-BIfl/fl mice and utilized the mice as a RAI model to elucidate the pathogenesis of RAI and GC therapy in sepsis. …

Environmental Toxicants And Human B Cells: Insights From Crispr Editing And Genomic Sequencing, Clayton Allex-Buckner

Browse all Theses and Dissertations

The human immunoglobulin heavy chain gene locus (IGH) has two 3 prime regulatory regions (3’IGHRR), each containing three enhancers (hs3, hs1.2, hs4). In animal models, the 3’IghRR regulates IgH expression and class switch recombination (CSR) to different Ig isotypes. The 3’IGHRR hs1.2 enhancer in humans is polymorphic in that an invariant sequence (IS) can be repeated one to four times in tandem. The hs1.2 polymorphism is of interest due to its association with several human autoimmune disorders and its potential sensitivity to exogenous substances such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin). In mouse models, TCDD inhibits the hs1.2 enhancer and 3’IghRR …

The Effect Of Larval Competition On Adult Life History Traits And The Immune Response Of Adult Cat Fleas (Ctenocephalides Felis), Piper N. Zellner, Lisa D. Brown

Honors College Theses

In holometabolous insects, conditions during the larval stage can affect the adult stage. For instance, in mosquitoes, reduced larval food and high density can make adults more susceptible to infection. Fleas (Siphonaptera), like mosquitoes, go through complete metamorphosis and have adult stages that exclusively feed on the blood of vertebrates, including humans. However, flea larvae have chewing mandibles and rely on nutrients from dried fecal matter containing vertebrate blood proteins. Their limited mobility and unique nutritional needs confine their development to specific areas, likely leading to frequent larval competition in natural conditions. Yet, the influence of larval density on the …

Presumptive Hepatogenous Photosensitization In Beef Cattle Winter Grazing A Cover Crop Containing Brassica Spp. Turnips, Matthew M. Hille, Scott A. Fritz, Breanna C. Brown

School of Veterinary and Biomedical Sciences: Faculty Publications

Over a period of ~2 wk, 5 adult beef cows developed severe necrotizing skin lesions on the face and neck shortly after being moved to a field with a cover crop of Brassica spp. turnips. We describe here the clinical signs, hematology, and serum chemistry results, as well as gross and histopathologic findings, from this outbreak. We made a presumptive diagnosis of Brassica-associated liver disease (BALD) based on the similarities in the history and diagnostic findings observed with previously reported cases of BALD from elsewhere in the world. BALD has not been reported previously in cattle in North America, …

Investigating The Role Of Bromodomain Proteins On Histone Post-Translational Modifications In Toxoplasma Gondii, Joshua Steven Berthiaume

Honors Theses and Capstones

Toxoplasma gondii is a prevalent pathogenic parasite that infects approximately 25 percent of the US population. For the parasite to successfully establish and maintain infection in its host, properly controlled regulation of gene expression is critical. One way Toxoplasma regulates gene expression is through modification of histone proteins that bind to DNA and can control gene accessibility. Acetylation is a modification that is added to histones that changes chromatin structure to enhance gene activation. Histone acetylation can also regulate gene expression by recruitment of important regulators such as bromodomain proteins (BDP). A previous study showed that loss of the bromodomain …