Immunoprophylaxis and Therapy Commons^™

Efficacy Of Probiotics In Decreasing Rates Of Necrotizing Enterocolitis And Sepsis In Preterm Neonates, Valisa K. Teekadharry

Theses and Graduate Projects

Background: The incidence of preterm infants developing serious infections is a common finding in many neonatal intensive care units. Probiotics have been a supplement that has been used by numerous people to improve the microbiota of the intestine for prevention of infection.

Purpose: The purpose of this literature review is to explore the efficacy of using probiotics in preterm infants for prevention of serious infections such as necrotizing enterocolitis (NEC) and sepsis.

Methods: A comprehensive literature review was conducted using Lindell Library, Pub Med, Science Direct and Google Scholar. Using the search terms probiotics, probiotics in premature infants, probiotics and …

The Role Of B Cell Activation State And Sex In Aryl Hydrocarbon Receptor Mediated Induction Of Chemokine Receptor 9 And Alpha4beta7 Expression In Vitro, Logan Bauerle

Master's Theses

Defense of mucosal tissues from microbial infection and allergy is reliant on continual production of antibodies. The aryl hydrocarbon receptor (AhR) is known to regulate B cell development and is associated with suppression of systemic humoral immunity. Recent attention has been paid to the role of the AhR in altering expression of cell adhesion molecules (CAMs). B cells express CAMs and chemokine receptors to migrate around the body for localized secretion of antibodies. AhR agonists promote B cell migration to the small intestine through upregulation of chemokine receptor 9 (CCR9) and integrin α₄β₇. Both the AhR …

Investigating Outcomes Of Emerging Treatments For Cerebral Palsy, Hannah Halt

University Honors College

Cerebral palsy presents a complex neurological challenge affecting movement and posture, with significant implications for individuals' quality of life. This essay provides a thorough examination of cerebral palsy, covering its prevalence, types, and associated health conditions. It explores current treatment modalities, including constraint-induced therapy, gaitfocused physical therapy, and cell-based therapies, highlighting their effectiveness and cost considerations. Ethical dilemmas in stem cell research for cerebral palsy are being discussed, alongside ongoing clinical trials and their potential impact. Through a multidisciplinary approach, this essay sheds light on the evolving landscape of cerebral palsy treatment, emphasizing the importance of early detection and intervention …

Stereotactic Ablative Radiotherapy With Or Without Immunotherapy For Early-Stage Or Isolated Lung Parenchymal Recurrent Node-Negative Non-Small-Cell Lung Cancer: An Open-Label, Randomised, Phase 2 Trial, Joe Y Chang, Steven H Lin, Wenli Dong, Zhongxing Liao, Saumil J Gandhi, Carl M Gay, Jianjun Zhang, Stephen G Chun, Yasir Y Elamin, Frank V Fossella, George Blumenschein, Tina Cascone, Xiuning Le, Jenny V Pozadzides, Anne Tsao, Vivek Verma, James W Welsh, Aileen B Chen, Mehmet Altan, Reza J Mehran, Ara A Vaporciyan, Stephen G Swisher, Peter A Balter, Junya Fujimoto, Ignacio I Wistuba, Lei Feng, J Jack Lee, John V Heymach

Faculty, Staff and Student Publications

BACKGROUND: Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small-cell lung cancer (NSCLC), but regional or distant relapses, or both, are common. Immunotherapy reduces recurrence and improves survival in people with stage III NSCLC after chemoradiotherapy, but its utility in stage I and II cases is unclear. We therefore conducted a randomised phase 2 trial of SABR alone compared with SABR with immunotherapy (I-SABR) for people with early-stage NSCLC.

METHODS: We did an open-label, randomised, phase 2 trial comparing SABR to I-SABR, conducted at three different hospitals in TX, USA. People aged 18 years or older …

Nanofabrication For Precision Vaccinology, Karen Zagorski

Theses & Dissertations

Vaccines are among the most effective and safe therapeutics known to mankind. Historically the approach to the creation of new vaccines has been dominated by empirical research, trial, and error. This thesis focuses on the more modern, rational approaches to vaccinology based on the current understanding of the inner workings of the immune system. We used nanotechnology for the generation of novel immunogens, addressed several challenges, and characterized the immune responses.

The preparation, characterization, and troubleshooting of several vaccines against dimeric amyloid beta are covered in chapters 4-6. Despite being ultimately unsuccessful, this part provided a deeper understanding of the …

Development Of Vaccines And Antivirals Against Zika Virus, Aryamav Pattnaik

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The re-emergence of Zika virus (ZIKV), an arbovirus, poses a major global human health concern because of its ability to cause congenital abnormalities and neurological diseases. While many candidate vaccines and antiviral drugs are in the developmental pipeline, none have been approved for use against ZIKV infection. This dissertation describes the characterization of one vaccine and two antiviral drug candidates against ZIKV infection. A bacterial ferritin-based nanoparticle vaccine, termed zDIII-F, is designed to display multiple copies of ZIKV E protein domain III on its surface. These stable nanoparticles are shown to induce robust antibody-mediated protection against lethal ZIKV infection in …

Sodium Pyruvate Ameliorates Influenza A Virus Infection In Vitro And In Vivo, Jessica M. Reel

Graduate Theses/Dissertations

Pyruvate is produced in duplicate at the end of glycolysis in addition to ATP and NADH. Pyruvate is the metabolite of choice in most cells, whether obtained exogenously or endogenously. Recently we found that the addition of pyruvate’s conjugate base, sodium pyruvate, to cell culture media dampened the immune response to influenza A virus (IAV) infection in cultured innate immune cells. Thus, I decided to investigate the mechanism and potential for treatment of IAV. In vitro using bone marrow derived macrophages that were infected with IAV we found that adding sodium pyruvate to the media decreased immune signaling pathways through …

The Intellectual Property Of Covid-19, Ana Santos Rutschman

All Faculty Scholarship

The response to COVID-19 is indissolubly tied to intellectual property. In an increasingly globalized world in which infectious disease pathogens travel faster and wider than before, the development of vaccines, treatments and other forms of medical technology has become an integral part of public health preparedness and response frameworks. The development of these technologies, and to a certain extent the allocation and distribution of resulting outputs, is informed by intellectual property regimes. These regimes influence the commitment of R&D resources, shape scientific collaborations and, in some cases, may condition the widespread availability of emerging technologies. As seen throughout this chapter, …

Histidine-Triad Hydrolases Provide Resistance To Peptide-Nucleotide Antibiotics., Eldar Yagmurov, Darya Tsibulskaya, Alexey Livenskyi, Marina Serebryakova, Yury I Wolf, Sergei Borukhov, Konstantin Severinov, Svetlana Dubiley

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The Escherichia coli microcin C (McC) and related compounds are potent Trojan horse peptide-nucleotide antibiotics. The peptide part facilitates transport into sensitive cells. Inside the cell, the peptide part is degraded by nonspecific peptidases releasing an aspartamide-adenylate containing a phosphoramide bond. This nonhydrolyzable compound inhibits aspartyl-tRNA synthetase. In addition to the efficient export of McC outside the producing cells, special mechanisms have evolved to avoid self-toxicity caused by the degradation of the peptide part inside the producers. Here, we report that histidine-triad (HIT) hydrolases encoded in biosynthetic clusters of some McC homologs or by standalone genes confer resistance to McC-like …

Exploring The Impact Of Pre-Exposure Prophylaxis Related To Sexual Behavior In College Men, Dalton J. Poe

Honors Undergraduate Theses

Pre-exposure prophylaxis (PrEP) is an effective tool for preventing human immunodeficiency virus (HIV) acquisition in sexually active at-risk individuals such as men who have sex with men (MSM). The purpose of this study is to examine factors associated with intent to engage in risky sexual behavior among HIV-negative college aged (18-24) MSM who are currently adherent to PrEP or who have expressed interest in the future adoption of PrEP. A multiracial/ethnic sample of 31 men expressing interest in the adoption of PrEP and 6 men currently taking PrEP completed a quantitative survey identifying key themes regarding attitudes towards PrEP and …

Development Of Novel Zika And Anthrax Viral Nanoparticle Vaccines, Elizabeth Henderson

KGI Theses and Dissertations

Vaccines protect against numerous infectious diseases and prevent millions of deaths annually, but there are still many infectious diseases for which no licensed vaccine exists. Developing a new vaccine requires balancing safety and efficacy, and viral nanoparticle (VNP) vaccines possess both of these characteristics. The work herein demonstrates how tobacco mosaic virus (TMV) nanoparticles can serve as a platform to create candidate vaccines for Zika virus (ZIKV) and anthrax. In the first study, a ZIKV-specific epitope was genetically fused to TMV to create a safe and inexpensive vaccine that proved highly immunogenic in mice and led to the discovery of …

A Mathematical Investigation On Tumor-Immune Dynamics: The Impact Of Vaccines On The Immune Response, Jonathan Quinonez, Neethi Dasu, Mahboobi Qureshi

Rowan-Virtua Research Day

Mathematical models analyzing tumor-immune interactions provide a framework by which to address specific scenarios in regard to tumor-immune dynamics. Important aspects of tumor-immune surveillance to consider is the elimination of tumor cells from a host’s cell-mediated immunity as well as the implications of vaccines derived from synthetic antigen. In present studies, our mathematical model examined the role of synthetic antigen to the strength of the immune system. The constructed model takes into account accepted knowledge of immune function as well as prior work done by de Pillis et al. All equations describing tumor-immune growth, antigen presentation, immune response, and interaction …

Tumor Immunotherapy: Mechanisms Of Acquired Resistance And Characterization Of Immune Related To Xicities, Ashvin Jaiswal

Dissertations and Theses (Open Access)

Tumor immunotherapy has shown very promising clinical benefit across an array of cancers; however, two major challenges remain unresolved in the field. First, many patients do not respond to therapy at all or relapse after a period of remission. Second, there are often dose-limiting immune related adverse effects associated with immunomodulation.

In order to understand the mechanisms employed by tumors to evade immunotherapeutic responses, we established a murine model of melanoma designed to elucidate the molecular mechanisms underlying immunotherapy resistance. Through multiple in vivo passages, we selected a B16 melanoma tumor line that evolved complete resistance to combination blockade of …

Tumor Surveillance Using Liquid Biome In Pediatric High Grade Gliomas, Erin Bonner, Eshini Panditharatna, Madhuri Kambhampati, Stefaan Van Gool, Wilfried Stuecker, Roger J. Packer, Javad Nazarian

GW Research Days 2016 - 2020

Immunotherapy is currently being used to treat pediatric brain cancer, though its efficacy in treating patients with diffuse intrinsic pontine glioma (DIPG), the deadliest pediatric brain tumor, has not been evaluated. MRI is the gold standard for monitoring tumor response to therapy, but is limited by pseudoresponse and psuedoprogression: post-treatment, immune cells infiltrate the primary tumor causing transient tumor enlargement, which falsely resembles tumor progression on MRI. Thus, it is critical to develop more accurate approaches to monitor tumor response to immunotherapy. Here, we use a liquid biopsy platform we have already established to monitor tumor response to therapy, to …

Systematic Review And Meta-Analysis: Tuberculosis, Tnfα Inhibitors, And Crohn's Disease, Brent L. Cao

Honors Undergraduate Theses

Inflammation is often a protective reaction against harmful foreign agents. However, in many disease conditions, the mechanisms behind the inflammatory response are poorly understood. Often times, the inflammation causes adverse effects, such as joint pain, abdominal pain, fever, fatigue, and loss of appetite. Thus, many treatments aim to inhibit the inflammatory response in order to control adverse symptoms. Such treatments include TNFα inhibitors. However, a major risk associated with drugs inhibiting tumor necrosis factor alpha (TNFα) is serious infection, including tuberculosis (TB).

Anti-TNFα therapy is used to treat patients with Crohn’s disease, for which the risk of tuberculosis may be …

Phytochemical Screening And Determination Of Antibacterial, Anti-Tumorigenic And Dna Protection Ability Of Root Extracts Of Saussurea Lappa, Sughra Arif Minhas, Fida Muhammad Khan, Fakhar-I- Abbas, Abu Ul Hassan Faiz

Journal of Bioresource Management

Saussurea lappa is a traditionally well-known plant for its medicinal uses in different indigenous systems of medicine. It is widely used in the treatment of asthma, ulcer, stomach problems and inflammatory diseases. In current study the phytochemical screening of S. lappa showed the presence of sesquiterpenes, anthraquinones, lignans, alkaloids, flavonoids, glycosides and steroids. Antimicrobial potential of subject plant was also investigated against three bacterial strains and maximum antibacterial activity was observed by CEE against S. aureus, CAE against P. aeruginosa, while CME, CEE, EAE and PEE showed almost same significant activity against E. coli. The CME (1000 …

Development Of C5ar-Targeted Nanoparticles For Delivery Of Vaccines, Shailendra Bharadwaj Tallapaka Venkata Sesha

Theses & Dissertations

Since the early attempts of Benjamin Jesty at inducing immunity against smallpox and the pioneering work of Edward Jenner, vaccination has been, and continues to remain, the principal method of protection from diseases. However, most of the successful vaccines have been against pathogens that do not have major mechanisms to evade the immune system. So far, many life-threatening diseases like hepatitis C, HIV infection, malaria etc., have been resistant to existing vaccination strategies. Thus, there is an urgent need to develop new vaccination strategies that can generate long-lived protective immunity against such pathogens.

The purpose of this thesis is to …

Impact Of A National Guideline On Antibiotic Selection For Hospitalized Pneumonia., Derek J Williams, Matthew Hall, Jeffrey S Gerber, Mark I Neuman, Adam L Hersh, Thomas V Brogan, Kavita Parikh, Sanjay Mahant, Anne J Blaschke, Samir S Shah, Carlos G Grijalva

Pediatrics Faculty Publications

BACKGROUND: We evaluated the impact of the 2011 Pediatric Infectious Diseases Society/Infectious Diseases Society of America pneumonia guideline and hospital-level implementation efforts on antibiotic prescribing for children hospitalized with pneumonia.

METHODS: We assessed inpatient antibiotic prescribing for pneumonia at 28 children's hospitals between August 2009 and March 2015. Each hospital was also surveyed regarding local implementation efforts targeting antibiotic prescribing and organizational readiness to adopt guideline recommendations. To estimate guideline impact, we used segmented linear regression to compare the proportion of children receiving penicillins in March 2015 with the expected proportion at this same time point had the guideline not …

Development Of Cellular Assays To Monitor Enzymatic And Biological Activity Of Cd73: A Key Modulator Of Anti-Tumor Immune Response, Alexandra Fanuka

Graduate School of Biomedical Sciences Theses and Dissertations

Ecto-5’-nucleotidase, known as CD73, is an extracellular enzyme that converts adenosine monophosphate (AMP) to adenosine and has recently been identified as a potential drug target for cancer immunotherapy. Its immunosuppressive effects, mediated by the activity of adenosine, are associated with higher rates of tumor invasion and metastasis, as well as poorer prognoses overall in many cancer types. CD73 is often co-expressed with ectonucleoside triphosphate diphosphohydrolase-1 (CD39), which catalyzes the conversion of adenosine triphosphate (ATP) to adenosine diphosphate (ADP), and ADP to AMP on the surface of tumor cells. Dual expression further propagates immunosuppressive effects of adenosine in the tumor microenvironment. …

Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez

Biology: Student Scholarship & Creative Works

ABSTRACT: The HIV-1 pandemic continues to thrive due to ineffective HIV-1 vaccines. Historically, the world’s most infectious diseases, such as polio and smallpox, have been eradicated or have come close to eradication due to the advent of effective vaccines. Highly active antiretroviral therapy is able to delay the onset of AIDS but can neither rid the body of HIV-1 proviral DNA nor prevent further transmission. A prophylactic vaccine that prevents the various mechanisms HIV-1 has to evade and attack our immune system is needed to end the HIV-1 pandemic. Recent advances in engineered nuclease systems, like the CRISPR/Cas9 system, have …

Hiv/Aids Care And Prevention Infrastructure In The U.S. Deep South, Susan S. Reif, Kristen Sullivan, Elena Wilson, Miriam Berger, Carolyn Mcallaster

Faculty Scholarship

No abstract provided.

Design And Testing Of Novel Anthrax Vaccines Utilizing A Tobacco Mosaic Virus Expression System, Ryan C. Mccomb

KGI Theses and Dissertations

Anthrax is a potentially fatal disease caused by the bacteria Bacillus anthracis. Infection and disease occur after spores gain entry into the body, germinate into vegetative bacteria, and produce toxin. Bacillus anthracis spores have been engineered as bioweapons and have been used repeatedly in warfare and terrorism to inflict casualties in military and civilian populations. Currently, only one vaccine has been approved for prevention of anthrax in the United States. This vaccine is an undefined product that is difficult to produce, requires a long vaccination schedule, and is reactogenic. Efforts to make an improved anthrax vaccine are being pursued. …

Berry Exotic: Alternative Therapies, Marissa Willimann

University Honors Program

Exotic berries are beginning to be investigated for their preventative properties such as antioxidants, anti-inflammatory, and hypocholesterolaemic levels. Berries consisting of these factors have been shown to reduce the risk for cardiovascular complications, acute or chronic diseases and other metabolic disease processes. These natural remedies are used to create a more holistic approach to medicine. The question raised is if the natural antioxidants and antiinflammatory properties that acaí, maqui, and blackthorn berries produce are more effective, less effective, or have no effect compared to medications that can be used. Research shows that reduction of glucose, total cholesterol and low density …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Role Of Viral And Host Factors In Influenza Virus Mediated Inhibition Of Interleukin-23, Ashish Tiwari

Theses and Dissertations--Veterinary Science

Influenza virus is one of the major respiratory pathogens of humans as well as animals, including equines. There is an increasing evidence that bacterial infections are the most common cause of the death during influenza. In horses also, secondary bacterial pneumonia can lead to death, and surviving horses may take up to six months for the complete recovery resulting in heavy economic loss to the equine industry. Interleukin (IL)-23 mediated innate immune response has been shown to protect the host from various respiratory bacterial infections. However, studies to investigate the role of host and viral factors in the regulation of …

Novel Imaging-Based Techniques Reveal A Role For Pd-1/Pd-L1 In Tumor Immune Surveillance In The Lung, Todd Bartkowiak

Dissertations and Theses (Open Access)

The binding of immune inhibitory receptor Programmed Death 1 (PD-1) on T cells to its ligand PD-L1 has been implicated as a major contributor to tumor induced immune suppression. Clinical trials of PD-L1 blockade have proven effective in unleashing therapeutic anti-tumor immune responses in a subset of patients with advanced melanoma, yet current response rates are low for reasons that remain unclear. Hypothesizing that the PD-1/PD-L1 pathway regulates T cell surveillance within the tumor microenvironment, we employed intravital microscopy to investigate the in vivo impact of PD-L1 blocking antibody upon tumor-associated immune cell migration. However, current analytical methods of intravital …

Cancer Immunotherapy Treatments, Shifra Sadowsky

The Science Journal of the Lander College of Arts and Sciences

Cancer is the second leading cause of death in American, with over half a million deaths from cancer reported in 2009. Cancer chemotherapy treatments were developed in the nineteen hundreds and remain the backbone of current treatments; however, they have some limitations. New immunotherapy cancer treatments, where biologic agents are given to patients to influence the body’s natural immune response, are being researched. Among these immunotherapy treatments are co-inhibition blockade of T cells, and combination blockade treatments together with chemotherapy treatment. This review will discuss T cell activation and the role of T cell coinhibitors such as CTLA-4 and PD-1 …

Immunological Mechanisms Of Extracorporeal Photopheresis In Cutaneous T Cell Lymphoma And Graft Versus Host Disease, Lisa Shiue

Dissertations and Theses (Open Access)

IMMUNOLOGICAL MECHANISMS OF EXTRACORPOREAL PHOTOPHERESIS IN CUTANEOUS T CELL LYMPHOMA AND GRAFT VERSUS HOST DISEASE

Publication No.___________

Lisa Harn-Ging Shiue, B.S.

Supervisory Professor: Madeleine Duvic, M.D.

Extracorporeal photopheresis (ECP) is an effective, low-risk immunomodulating therapy for leukemic cutaneous T cell lymphoma (L-CTCL) and graft versus host disease (GVHD), but whether the mechanism(s) of action in these two diseases is (are) identical or different is unclear. To determine the effects of ECP in vivo, we studied regulatory T cells (T-regs), cytotoxic T lymphocytes (CTLs), and dendritic cells (DCs) by immunofluorescence flow cytometry in 18 L-CTCL and 11 GVHD patients before …

Premature Induction Of An Immunosuppressive Regulatory T Cell Response During Acute Simian Immunodeficiency Virus Infection, Jacob D. Estes, Qingsheng Li, Matthew R. Reynolds, Stephen W. Wietgrefe, Lijie Duan, Timothy Schacker, Louis J. Picker, David I. Watkins, Jeffrey D. Lifson, Cavan Reilly, John V. Carlis, Ashley T. Haase

Qingsheng Li Publications

Here we report the results of an investigation into the possibility that one mechanism responsible for the establishment of persistent human immunodeficiency virus infection is an early regulatory T (T_reg) cell response that blunts virus- specific responses. Using the simian immunodeficiency virus (SIV)–infected rhesus macaque model, we show that, indeed, viral replication and immune activation in lymphatic tissue drive a premature immunosuppressive response, with dramatic increases in the frequencies of CD4⁺CD25⁺FOXP3⁺ Treg cells, transforming growth factor–β1⁺ cells, interleukin–10+ cells, and indoleamine 2,3-dioxygenase+CD3⁺ cells.When we compared SIV infection with rhesus cytomegalovirus (RhCMV) …