Medicine and Health Sciences Commons^™

Active And Passive Immunization With An Anti-Methamphetamine Vaccine Attenuates The Behavioral And Cardiovascular Effects Of Methamphetamine, Colin N. Haile, Kurt J. Varner, Xia Huijing, Reetakshi Arora, Frank M. Orson, Thomas R. Kosten, Therese A. Kosten

School of Medicine Faculty Publications

Background: Methamphetamine use disorder (MUD) is a growing health concern with no FDA-approved treatment. The present series of studies build upon our previous work developing an anti-methamphetamine (MA) vaccine for MUD. We determined the effects of a formulation that included tetanus-toxoid (TT) conjugated to succinyl-methamphetamine (TT-SMA) adsorbed onto aluminum hydroxide (alum) in combination with the novel Toll-Like Receptor-5 agonist, entolimod. Methods: Mice were vaccinated (0, 3, 6 weeks) with TT-SMA+alum and various doses of entolimod to determine an optimal dose for enhancing immunogenicity against MA. Functional effects were then assessed using MA-induced locomotor activation in mice. Experiments using passive immunization …

Sars-Cov-2 Invasion And Pathological Links To Prion Disease, Walter J. Lukiw, Vivian R. Jaber, Aileen I. Pogue, Yuhai Zhao

School of Medicine Faculty Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 disease, is a highly infectious and transmissible viral pathogen that continues to impact human health globally. Nearly ~600 million people have been infected with SARS-CoV-2, and about half exhibit some degree of continuing health complication, generically referred to as long COVID. Lingering and often serious neurological problems for patients in the post-COVID-19 recovery period include brain fog, behavioral changes, confusion, delirium, deficits in intellect, cognition and memory issues, loss of balance and coordination, problems with vision, visual processing and hallucinations, encephalopathy, encephalitis, neurovascular or cerebrovascular insufficiency, and/or …

Pre-Exposure To Mrna-Lnp Inhibits Adaptive Immune Responses And Alters Innate Immune Fitness In An Inheritable Fashion, Zhen Qin, Aurélie Bouteau, Christopher Herbst, Botond Z. Igyártó

Department of Microbiology and Immunology Faculty Papers

Hundreds of millions of SARS-CoV-2 mRNA-LNP vaccine doses have already been administered to humans. However, we lack a comprehensive understanding of the immune effects of this platform. The mRNA-LNP-based SARS-CoV-2 vaccine is highly inflammatory, and its synthetic ionizable lipid component responsible for the induction of inflammation has a long in vivo half-life. Since chronic inflammation can lead to immune exhaustion and non-responsiveness, we sought to determine the effects of pre-exposure to the mRNA-LNP on adaptive immune responses and innate immune fitness. We found that pre-exposure to mRNA-LNPs or LNP alone led to long-term inhibition of the adaptive immune response, which …

Is Strongyloides Stercoralis Hyperinfection Induced By Gglucocorticoids A Result Of Both Suppressed Host Immunity And Altered Parasite Genetics?, De'broski R Herbert, Jonathan D C Stoltzfus, Heather L Rossi, David Abraham

Department of Microbiology and Immunology Faculty Papers

The gastrointestinal (GI) nematode Strongyloides stercoralis (S.s.) causes human strongyloidiasis, a potentially life-threatening disease that currently affects over 600 million people globally. The uniquely pernicious aspect of S.s. infection, as compared to all other GI nematodes, is its autoinfective larval stage (L3a) that maintains a low-grade chronic infection, allowing undetectable persistence for decades. Infected individuals who are administered glucocorticoid therapy can develop a rapid and often lethal hyperinfection syndrome within days. Hyperinfection patients often present with dramatic increases in first- and second-stage larvae and L3a in their GI tract, with L3a widely disseminating throughout host organs leading to sepsis. How …

Homeostasis Of Cell Wall Integrity Pathway Phosphorylation Is Required For The Growth And Pathogenicity Of Magnaporthe Oryzae, Yongchao Cai, Xinyu Liu, Lingbo Shen, Nian Wang, Yangjie He, Haifeng Zhang, Ping Wang, Zhengguang Zhang

School of Graduate Studies Faculty Publications

The cell wall provides a crucial barrier to stress imposed by the external environment. In the rice blast fungus Magnaporthe oryzae, this stress response is mediated by the cell wall integrity (CWI) pathway, consisting of a well-characterized protein phosphorylation cascade. However, other regulators that maintain CWI phosphorylation homeostasis, such as protein phosphatases (PPases), remain unclear. Here, we identified two PPases, MoPtc1 and MoPtc2, that function as negative regulators of the CWI pathway. MoPtc1 and MoPtc2 interact with MoMkk1, one of the key components of the CWI pathway, and are crucial for the vegetative growth, conidial formation, and virulence of M. …

Microbiome Dynamics During Chemoradiation Therapy For Anal Cancer, Daniel Lin, Molly B. El Alam, Joseph Abi Jaoude, Ramez Kouzy, Jae L. Phan, Jacob H. Elnaggar, Brianna Resendiz, Andrea Y.Delgado Medrano, Erica J. Lynn, Nicholas D. Nguyen, Sonal S. Noticewala, Geena G. Mathew, Emma B. Holliday, Bruce D. Minsky, Prajnan Das, Van K. Morris, Cathy Eng, Melissa P. Mezzari, Joseph F. Petrosino, Nadim J. Ajami, Ann H. Klopp, Cullen M. Taniguchi, Lauren E. Colbert

School of Graduate Studies Faculty Publications

Purpose: Patients with localized squamous cell carcinoma of the anus (SCCA) who experience treatment toxicity or recurrences have few therapeutic options. Investigation into the microbiome's influence on treatment toxicity and its potential use as a predictive biomarker could improve these patients’ outcomes. Our study presents the first longitudinal characterization of the SCCA tumor microbiome and its associations with treatment-related toxicities. Methods and Materials: This prospective cohort study included patients with nonmetastatic SCCA receiving standard-of-care chemoradiation therapy. Anorectal swabs of the tumor site were collected before, during, and after treatment. Patient-reported quality-of-life metrics were collected at similar time points. 16S rRNA …

Defining The Cooperation Between Mhc-I And Mhc-Ii Neoantigen-Driven T Cell Responses To Develop Effective Personalized Immunotherapies, Charmelle Williams

Dissertations & Theses (Open Access)

Immune checkpoint therapy (ICT) (e.g. anti-CTLA-4 (α-CTLA-4), anti-PD-1 (α-PD-1)) enables durable T cell-dependent anti-tumor immunity in certain cancer patients. Since a subset of patients respond to ICT, this work aims at developing a more in-depth understanding of T-cell responses to MHC class I (MHC-I) and MHC class II (MHC-II) tumor antigens that are derived from aberrant expression of non-mutant antigens or driver and passenger somatic alterations that can function as tumor neoantigens. We used a poorly immunogenic Braf^v600e Pten^-/- Cdkn2a^-/- YUMM1.7 (Y1.7) murine melanoma line with a paucity of endogenous neoantigens that is unresponsive to ICT, and …

V2 Hotspot Optimized Mva Vaccine Expressing Stabilized Hiv-1 Clade C Envelope Gp140 Delays Acquisition Of Heterologous Clade C Tier 2 Challenges In Mamu-A*01 Negative Rhesus Macaques, Tiffany M. Styles, Sailaja Gangadhara, Pradeep B.J. Reddy, Anusmita Sahoo, Ayalensh Shiferaw, Sarah Welbourn, Pamela A. Kozlowski, Cynthia A. Derdeyn, Vijayakumar Velu, Rama Rao Amara

School of Graduate Studies Faculty Publications

Stabilized HIV envelope (Env) trimeric protein immunogens have been shown to induce strong autologous neutralizing antibody response. However, there is limited data on the immunogenicity and efficacy of stabilized Env expressed by a viral vector-based immunogen. Here, we compared the immunogenicity and efficacy of two modified vaccinia Ankara (MVA) vaccines based on variable loop 2 hotspot (V2 HS) optimized C.1086 envelope (Env) sequences, one expressing the membrane anchored gp150 (MVA-150) and the other expressing soluble uncleaved pre-fusion optimized (UFO) gp140 trimer (MVA-UFO) in a DNA prime/MVA boost approach against heterologous tier 2 SHIV1157ipd3N4 intrarectal challenges in rhesus macaques (RMs). Both …

"Don't Look Up" Your Science-Herd Immunity Or Herd Mentality?, Botond Z Igyártó

Department of Microbiology and Immunology Faculty Papers

This analysis piece will attempt to examine some of the critical pandemic-related measures implemented in the United States from an immunological perspective and pinpoint caveats that should have been considered before their implementation. I also discuss alternative measures grounded in scientific data that were not thoroughly explored and likely could have helped fight the pandemic.

Solid-State Nmr Analysis Of Unlabeled Fungal Cell Walls From Aspergillus And Candida Species, Liyanage D. Fernando, Malitha C. Dickwella Widanage, S. Chandra Shekar, Frederic Mentink-Vigier, Ping Wang, Sungsool Wi, Tuo Wang

School of Medicine Faculty Publications

Fungal infections cause high mortality in immunocompromised individuals, which has emerged as a significant threat to human health. The efforts devoted to the development of antifungal agents targeting the cell wall polysaccharides have been hindered by our incomplete picture of the assembly and remodeling of fungal cell walls. High-resolution solid-state nuclear magnetic resonance (ss NMR) studies have substantially revised our understanding of the polymorphic structure of polysaccharides and the nanoscale organization of cell walls in Aspergillus fumigatus and multiple other fungi. However, this approach requires 13C/15N-enrichment of the sample being studied, severely restricting its application. Here we employ the dynamic …

Real-World Third Covid-19 Vaccine Dosing And Antibody Response In Patients With Hematologic Malignancies, Michael A. Thompson, Sigrun Hallmeyer, Veronica E. Fitzpatrick, Yunqi Liao, Michael P. Mullane, Stephen C. Medlin, Kenneth Copeland, James L. Weese

Journal of Patient-Centered Research and Reviews

Purpose: This study sought to describe the changes in immune response to a third dose of either Pfizer’s or Moderna’s COVID-19 mRNA vaccine (3V) among patients with hematologic malignancies, as well as associated characteristics

Methods: This retrospective cohort study analyzed pre-3V and post-3V data on 493 patients diagnosed with hematologic malignancies across a large Midwestern health system between August 28, 2021, and November 1, 2021. For antibody testing, S1 spike antigen of the SARS-CoV-2 virus titer was used to determine serostatus.

Results: Among 493 participants, 274 (55.6%) were seropositive both pre- and post-3V (+/+) while 115 (23.3%) seroconverted to positive …

B- And T-Cell Subset Abnormalities In Monogenic Common Variable Immunodeficiency, Saba Fekrvand, Shaghayegh Khanmohammadi, Hassan Abolhassani, Reza Yazdani

Department of Neurology Faculty Papers

Common variable immunodeficiency (CVID) is a heterogeneous group of inborn errors of immunity characterized by reduced serum concentrations of different immunoglobulin isotypes. CVID is the most prevalent symptomatic antibody deficiency with a broad range of infectious and non-infectious clinical manifestations. Various genetic and immunological defects are known to be involved in the pathogenesis of CVID. Monogenic defects account for the pathogenesis of about 20-50% of CVID patients, while a variety of cases do not have a defined genetic background. Deficiencies in molecules of B cell receptor signaling or other pathways involving B-cell development, activation, and proliferation could be associated with …

Genomic Features Underlie The Co-Option Of Sva Transposons As Cis-Regulatory Elements In Human Pluripotent Stem Cells, Samantha M Barnada, Andrew Isopi, Daniela Tejada-Martinez, Clément Goubert, Sruti Patoori, Luca Pagliaroli, Mason Tracewell, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

Domestication of transposable elements (TEs) into functional cis-regulatory elements is a widespread phenomenon. However, the mechanisms behind why some TEs are co-opted as functional enhancers while others are not are underappreciated. SINE-VNTR-Alus (SVAs) are the youngest group of transposons in the human genome, where ~3,700 copies are annotated, nearly half of which are human-specific. Many studies indicate that SVAs are among the most frequently co-opted TEs in human gene regulation, but the mechanisms underlying such processes have not yet been thoroughly investigated. Here, we leveraged CRISPR-interference (CRISPRi), computational and functional genomics to elucidate the genomic features that underlie SVA domestication …

Identification Of Therapeutic Targets For Th17 Cell-Mediated Diseases, Jin Wang

Theses and Dissertations (ETD)

Hypersensitivity and autoimmune diseases are complex synergistic effect of environmental, genetic and other factors. T helper 17 (Th17) cells play a critical role in the immune pathology. Th17 cells are a group of specialized CD4+ T cells with potential pro-inflammatory function which are different from other T cells such as T helper 1 (Th1) cells or T helper 2 (Th2) cells. Th17 cell development and differentiation processes are strictly regulated through complex pathways. Th17 cells are characterized by secreting cytokines such as IL-17 and IL-22. Studies have shown that Th17 cells and IL-17 have been implicated in the pathogenesis of …

Host-Pathogen Interactions During Leptospirosis In Male C3h/Hej Mice, Advait Bhaskar Shetty

Theses and Dissertations (ETD)

Leptospirosis is a zoonotic disease transmitted from reservoir hosts like rodents to other animals and humans, who are incidental hosts. This infection is prevalent in the areas of Southeast Asia, Africa and South America. Inactivated Leptospira serovars vaccines are available in endemic areas but they have certain limitations such as serovar specificity and short-term protection. Antibiotics are effective treatment strategies useful at least during early stages of infection. Early diagnosis of Leptospirosis is difficult due to lack of accessible laboratory and point of care tests and due to clinical similarities with other diseases. Thus, it is important to understand host-Leptospira …

Targeting Myeloid Protein Kinase C Signaling To Overcome Immune Suppression And Improve Immunotherapy In Cancer, Mehdi Chaib

Theses and Dissertations (ETD)

Checkpoint immunotherapy unleashes T cell antitumor potential which has revolutionized cancer treatment showing unprecedented long-term responses. However, most patients do not respond to immunotherapy which often correlates with a dysfunctional or immunosuppressive myeloid compartment. Immunosuppressive myeloid cells comprise Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) and can suppress T cells via production of immunosuppressive factors. Conversely, efficient cytotoxic T cell priming is dependent on the ability of antigen-presenting cells (APCs), mainly conventional dendritic cells (cDCs) and macrophages, to present or cross-present tumor antigens to T cells. Thus, targeting immunosuppressive myeloid cells while simultaneously enhancing APCs represents a promising strategy …

A Single Dose Of The Deactivated Rabies-Virus Vectored Covid-19 Vaccine, Coravax, Is Highly Efficacious And Alleviates Lung Inflammation In The Hamster Model, Drishya Kurup, Christoph Wirblich, Leila Zabihi Diba, Rachael Lambert, Megan Watson, Noor Shaikh, Holly Ramage, Charalambos Solomides, Matthias J Schnell

Department of Microbiology and Immunology Faculty Papers

Without sufficient herd immunity through either vaccination or natural infection, the coronavirus disease 2019 pandemic is unlikely to be controlled. Waning immunity with the currently approved vaccines suggests the need to evaluate vaccines causing the induction of long-term responses. Here, we report the immunogenicity and efficacy of our adjuvanted single-dose Rabies-vectored SARS-CoV-2 S1 vaccine, CORAVAX, in hamsters. CORAVAX induces high SARS-CoV-2 S1-specific and virus-neutralizing antibodies (VNAs) that prevent weight loss, viral loads, disease, lung inflammation, and the cytokine storm in hamsters. We also observed high Rabies VNA titers. In summary, CORAVAX is a promising dual-antigen vaccine candidate for clinical evaluation …

Antigen Staining For Detection Of Muc13 And Muc16 Expression In Carcinoma Tissue, Jose A. Benitez

MEDI 9331 Scholarly Activities Clinical Years

MUC13 and MUC16 are epithelial expressed proteins implicated in various carcinomas. Overexpression of these biomarkers appear to play a role in tumor growth; this discovery has paved a road for multiple studies discussing the potential of targeting mucin proteins and optimize immunotherapy approaches against carcinomas. Our study serves to investigate the level of expression of MUC13 and MUC16 in cancerous and normal tissue and to discuss the implications our findings may have for the utilization of these biomarkers for cancer therapy.

A Within-Host Modeling Framework For Sars-Cov-2 Infection To Support Vaccine Strategies, Morgan Rose, Rachel Jennings, Jeffry Schroeter

Biology and Medicine Through Mathematics Conference

No abstract provided.

Cathelicidin Anti-Microbial Peptide (Camp) Is Toxic During Neonatal Influenza Virus Infection, Nneka Ugwu

St. Chris Research Day

No abstract provided.

Rates And Perceptions Of Covid-19 Vaccination From University Of Mississippi Students, Josie Parham

Honors Theses

The trials, tribulations and triumphs of the global COVID-19 pandemic are impacted by and are a product of behaviors that occur at the level of nations, states, cities and, ultimately, communities. In the wake of the development of safe and effective vaccines against SARS-CoV2, the virus responsible for the pandemic, the significance of the vaccine is closely linked to the number of individuals that receive the vaccine. To date, surveys have measured sizable variations in vaccination rates between nations, states, cities, and communities. Focusing on events that have transpired in one such local community, the present study (i) measured the …

Erα As A Modulator Of The Sle1b Lupus Susceptibility Locus And B Cell Receptor Signaling, Jared H. Graham

Theses & Dissertations

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by loss of immune tolerance and the production of anti-nuclear autoantibodies. 90% of lupus patients are women, and this sex bias is due to the actions of estrogens, which promote lupus pathogenesis. Our lab has shown that estrogen receptor alpha (ERα) mediates the effect of estrogens in lupus and that ERa acts in a B cell intrinsic manner to promote the development of autoantibodies and SLE. Genetic factors also contribute to lupus. One major lupus susceptibility locus, Sle1, controls loss of tolerance and autoantibody development as well as immune cell …

Psychological Trauma Alters T-Lymphocyte Inflammation And Redox Through Sympathetic Mechanisms, Safwan K. Elkhatib

Theses & Dissertations

Posttraumatic stress disorder (PTSD) is a devastating psychiatric disorder characterized by distinctive symptom clusters, including intrusive memories (i.e., flashbacks), avoidance of related stimuli, affective changes, and hyperarousal. Strikingly, patients with PTSD face a significantly increased risk for a number of inflammation-driven pathologies, ranging from cardiovascular to autoimmune disease. Yet, the exact etiology of this increased risk remains unknown. The immune system is known to be strongly influenced by the sympathetic nervous system, and sympathetic overactivity is a hallmark of PTSD. Lymphoid organs, such as the spleen, are richly innervated by sympathetic nerve fibers which terminate near adaptive immune …

A Suspected Case Of Vaccine Induced Thrombosis With Thrombocytopenia Following Sars Cov2 Vaccine, Maryam Soliman

Rowan-Virtua Research Day

With the new development of the SARS-CoV vaccine and the majority of the population receiving this vaccine, it is important to recognize some of the rare side effects associated with it.

VITT is a rare complication of the COVID vaccine

Diagnostic criteria: COVID vaccine 4-24 days prior to symptom onset, any venous or arterial thrombosis, thrombocytopenia <150, positive PF4 HIT ELISA, markedly elevated D-dimer >4x ULN.

Vaccine Induced Thrombosis with Thrombocytopenia is a potentially life-threatening diagnosis that must be recognized and treated correctly to prevent poor outcomes.

Atr-Mediated Cd47 And Pd-L1 Upregulation Restricts Radiotherapy-Induced Immune Priming And Abscopal Responses In Colorectal Cancer, Cheng-En Hsieh, Cheng-En Hsieh

Dissertations & Theses (Open Access)

Radiotherapy of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically. However, incidences of abscopal tumor remission are extremely rare, and the post-irradiation immune escape mechanisms in CRC remain elusive. We report that CRC cells utilize a common DNA repair signaling pathway — ATR/Chk1/STAT3 — to upregulate both CD47 and PD-L1 in response to radiotherapy, which through engagement of SIRPα and PD-1 suppresses the capacity of antigen-presenting cells to phagocytose them thereby preventing TAA cross-presentation and innate immune activation. This post-irradiation CD47 and PD-L1 upregulation can be observed across various human solid tumor cells. Concordantly, …

The Role Of Obesity In Macrophage-Mediated Mechanisms Promoting Early-Onset Colon Cancer., Katharina Marietta Scheurlen

Electronic Theses and Dissertations

Early-onset colon cancer (EOCC) is a leading cause of cancer death among people younger than 50 years of age in the United States and is associated with metabolic dysfunction and obesity. Anti-inflammatory tumor-associated macrophages (TAM) and low Peroxisome Proliferator Activated Receptor Gamma (PPARγ) gene expression in colon cancer (CC) tissue promote tumor progression and decreased patient survival. Obesity-related hormones, such as leptin and adiponectin, have the potential to affect gene expression in TAM to promote CC progression and thereby link obesity and EOCC. The aim of this project was to identify target genes in human CC and to investigate the …

T Cell Therapy: Underlying Mechanisms And Current Advancements, Griffin Mccloy

Senior Honors Theses

As the second leading cause of death in 2016, cancer is one of the most serious diseases facing the world today. T cell therapy is a current area of research attempting to address the disease with two primary division: CAR-T and TCR-T cell therapy. The immune system naturally produces T lymphocytes to aid in the recognition and removal of cells infected with viruses or transformed into cancer. Under normal circumstances, T lymphocytes identify and destroy cancerous cells; however, some cancerous cell types can evade this system. With the use of genetic editing technology, T lymphocytes can gain the ability to …

Evaluating The Validity Of Restrictions On Blood Donation Eligibility For Men Who Have Sex With Men (Msm) In The United States, France, And Switzerland, Swathi Gorantla

Independent Study Project (ISP) Collection

For the first time in a decade, the number of new human immunodeficiency virus (HIV) diagnoses is higher for heterosexual people compared to gay and bisexual men (Florêncio, 2022). Additionally, in the United States, the American Red Cross has declared a national blood crisis due to the nationwide shortage of donated blood. During this crisis, charged with the new information on HIV diagnosis rates, many advocates for the Lesbian, Gay, Bisexual, Transgender, Queer (LGBTQ+) community question why discriminatory policy surrounding gay and bisexual men donating still exist around the world. These policies are changing worldwide – several European countries have …

Variations In Antibody Response To Aspergillus Fumigatus Inhalation In Mice, Andrea Wells

Student Academic Conference

Studies have configured immunological responses to Aspergillus fumigatus in mice, leading to advanced understandings. However, the comparisons of the immune responses between juvenile (younger than 6 weeks) male and female C57BL/6J mice after A. fumigatus exposure, remains uninvestigated. In this study, we intranasally inoculated 3 week old male and female mice with Aspergillus fumigatus spores dilution of 2 106spores per 40 l. They were exposed to the allergen once a week for 8 consecutive weeks and euthanized on day 28 post the last inoculation. As compared to our last report, we increased the sample size for each group in this …

Medical Factors Associated With Caregiver Intention To Vaccinate Their Children Against Covid-19, Thao-Ly Phan, Paul T Enlow, Michael King, Amanda M Lewis, Anne E Kazak, Jonathan M Miller

Department of Medicine Faculty Papers

Objective: To describe medical factors that are associated with caregiver intention to vaccinate their children against COVID-19.

Methods: We conducted a cross-sectional study of families receiving primary care in a mid-Atlantic pediatric healthcare system, linking caregiver-reported data from a survey completed March 19 to April 16, 2021 to comprehensive data from the child's EHR.

Results: 513 families were included (28% Black, 16% Hispanic, 44% public insurance, 21% rural, child age range 0-21 years). 44% of caregivers intended to vaccinate their children against COVID-19, while 41% were not sure and 15% would not. After adjusting for socio-demographics, the only medical factors …