Medical Immunology Commons^™

Prevalence Of Infectious Diseases Among 6078 Individuals With Down Syndrome In The United States, Veronica Fitzpatrick, Anne Rivelli, Sagar Chaudhari, Laura Chicoine, Gengjie Jia, Andrey Rzhetsky, Brian Chicoine

Journal of Patient-Centered Research and Reviews

A recent disease prevalence study of the largest documented Down syndrome (DS) cohort in the United States strongly suggested significant disparity in general infectious disease conditions among individuals with DS versus those without DS. In this follow-up retrospective analysis, we explored these differences in greater detail by calculating prevalence of 52 infectious diseases, across 28 years of data among 6078 individuals with DS and 30,326 age- and sex-matched controls, abstracted from electronic medical records within a large Midwestern health system. We found that the DS cohort had higher prevalence of pneumonias (including aspiration, viral, bacterial, pneumococcal, and unspecified/atypical); otitis externa; …

Seroprevalence Of Covid-19 Igg Antibody In Resident And Fellow Physicians In Milwaukee, Wisconsin: Analysis Of A Cross-Sectional Survey, Dennis J. Baumgardner, Alexander Schwank, Jessica J. F. Kram, Wilhelm Lehmann, Jacob Bidwell, Tricia La Fratta, Kenneth Copeland

Journal of Patient-Centered Research and Reviews

Purpose: Medical trainees are likely at differential risk of exposure to COVID-19 per respective clinical activity. We sought to determine the seroprevalence of COVID-19 antibody (Ab) among resident and fellow physicians with varying degrees of exposure to COVID-19.

Methods: A cross-sectional study of Milwaukee-based resident and fellow physicians, encompassing December 2019–June 2020, was conducted. Relevant variables of interest were ascertained by survey and payroll data, and Abbott ARCHITECT Ab test (index cut-off of ≥ 1.4) was performed. Descriptive statistics were generated, with 95% CI calculated for the study’s primary outcome of seroprevalence.

Results: Among survey respondents (92 of 148, 62%), …

Anti-Cd40 Antibody Fused To Cd40 Ligand Is A Superagonist Platform For Adjuvant Intrinsic Dc-Targeting Vaccines., Valentina Ceglia, Sandra Zurawski, Monica Montes, Mitchell Kroll, Aurélie Bouteau, Zhiqing Wang, Jerome Ellis, Botond Z Igyártó, Yves Lévy, Gerard Zurawski

Department of Microbiology and Immunology Faculty Papers

CD40 is a potent activating receptor expressed on antigen-presenting cells (APCs) of the immune system. CD40 regulates many aspects of B and T cell immunity via interaction with CD40L expressed on activated T cells. Targeting antigens to CD40 via agonistic anti-CD40 antibody fusions promotes both humoral and cellular immunity, but current anti-CD40 antibody-antigen vaccine prototypes require co-adjuvant administration for significant in vivo efficacy. This may be a consequence of dulling of anti-CD40 agonist activity via antigen fusion. We previously demonstrated that direct fusion of CD40L to anti-CD40 antibodies confers superagonist properties. Here we show that anti-CD40-CD40L-antigen fusion constructs retain strong …

Fbxw7-Mediated Erk3 Degradation Regulates The Proliferation Of Lung Cancer Cells, Hyun-Jung An, Cheol-Jung Lee, Ga-Eun Lee, Youngwon Choi, Dohyun Jeung, Weidong Chen, Hye Suk Lee, Han Chang Kang, Joo Young Lee, Dae Joon Kim

School of Medicine Publications and Presentations

Extracellular signal-regulated kinase 3 (ERK3) is an atypical member of the mitogen-activated protein kinase (MAPK) family, members of which play essential roles in diverse cellular processes during carcinogenesis, including cell proliferation, differentiation, migration, and invasion. Unlike other MAPKs, ERK3 is an unstable protein with a short half-life. Although deubiquitination of ERK3 has been suggested to regulate the activity, its ubiquitination has not been described in the literature. Here, we report that FBXW7 (F-box and WD repeat domain-containing 7) acts as a ubiquitination E3 ligase for ERK3. Mammalian two-hybrid assay and immunoprecipitation results demonstrated that ERK3 is a novel binding partner …

Breadth Of Vaccinated Cancer Patient Humoral Response To Sars-Cov-2 Spike Protein And Rbd Variants, Julia Corman, Joey Breckenridge Jr., Adrienne M. Bushau-Sprinkle, Krystal T. Hamorsky, Joshua L. Fuqua

Posters-at-the-Capitol

SARS-CoV-2, the virus responsible for the COVID-19 of which several variants have emerged, such as the B.1.351 SARS-CoV-2 variant. The Receptor Binding Domain (RBD), located within the Spike protein is an immunogenic epitope for potent neutralizing antibodies. Current mRNA vaccines encode for the Spike protein, allowing the body to build antigen-specific antibodies. Assays measuring protective antibodies are essential to manage the COVID-19 pandemic and can be used as a platform for variant screening. RBD-foldon 2.2 is a novel antigen produced by fusing RBD with the trimerization domain Fibritin from Bacteriophage T4. Its amino acid sequence is based on the original …

Effectiveness Of Stricter Vaccine Mandates In Public Schools And Childcare Centers, Anna Ferentinos

Emerging Writers

Vaccines have been a controversial and frequently discussed topic the last two years due to the COVID-19 pandemic. The amount of readily available information on the internet - accurate or not – has led to many theories and opinions on whether to vaccinate and why, or why not. This article discusses these theories, as well as the benefits and consequences of vaccine mandates, with the help of examples from other countries. The author argues that a federal vaccine mandate should be implemented in the United States of America so as to encourage parents to protect children through scheduled immunizations.

Sodium Hydrogen Exchanger 1 Enhances Antitumor Activity Of Nk-92 Natural Killer Cells, Yaoyu Gong

Publicly Accessible Penn Dissertations

Adoptive cell transfer immunotherapy has remarkable efficacy against some hematological malignancies. However, its efficacy in solid tumors is limited by the adverse tumor microenvironment (TME) conditions, most notably that acidity inhibits T and NK cell mTORC1 activity and impairs cytotoxicity. In several reported studies, systemic buffering of tumor acidity enhanced the efficacy of immune checkpoint inhibitors. Paradoxically, we found in a Myc-inducible hepatocellular carcinoma model that buffering increased tumor mTORC1 activity, negating inhibition of tumor growth by anti-PD1 treatment. To avoid such adverse effects of systemic buffering favoring tumor growth, we overexpressed activated RHEB in the human NK-92 cell line, …

Central Control Of Pain And Inflammation Through A Hunger Circuit, Michelle Lynne Klima

Publicly Accessible Penn Dissertations

Homeostasis is established through bidirectional communication between the periphery and the central nervous system. To maintain homeostasis, some biological drives can become prioritized over others. This changing balance between biological drives encourages peak performance and survival. However, when homeostasis is disturbed, chronic inflammatory diseases such as obesity, chronic pain, and arthritis can arise. We became interested in understanding if competing biological drives could be leveraged for therapeutic purposes. Food restriction inhibits inflammation; therefore, we explored how hunger and feeding neural circuits affect responses to noxious agents. Our first study investigated the role of hunger to alleviate pain behavior. We found …

Development Of Novel Vaccination Strategies Against Emerging Bunyaviruses, Tomaz Manzoni

Publicly Accessible Penn Dissertations

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a highly pathogenic emergent bunyavirus. First isolated in 2009 in China, SFTSV is now endemic to several east Asian countries where high case fatality ratios of 6-30% are reported. The primary tick vector of SFTSV, Haemaphysalis longicornis, has a large range and is a well reported invasive species throughout the world. This, in addition to SFTSV’s ability to spread in the absence of its vector in nosocomial and veterinary settings, suggests SFTSV is well suited to cause widespread lethal outbreaks. Currently no vaccines or therapeutics against SFTSV exist, prompting health agencies to …

Deciphering The Heterogeneity Of Hiv Reservoir Immunology: A Single-Cell Perspective, Vincent Huang Wu

Publicly Accessible Penn Dissertations

Since its initial documentation in 1981, the acquired immunodeficiency syndrome (AIDS) epidemic has impacted more than 70 million people. As the causative agent of AIDS, human immunodeficiency virus (HIV) is a retrovirus that integrates a copy of its viral genome (termed provirus) into the genome of target cells known as CD4+ T cells. With antiretroviral therapy (ART), persons living with HIV (PLWH) can suppress viral replication and prevent progression to AIDS. However, ART is usually a lifelong requirement as interruption can lead to viral rebound via transcription at the integrated viral genome. During early HIV infection, some infected cells can …

Establishment And Verification Of A Sars Cov2 Antibody Detection Assay Comparing Venous And Mitra Samples, Stephen C. Mayer

Theses and Dissertations--Medical Sciences

During the COVID-19 pandemic in 2020, the need for highly-specific, wide-spread, and rapid serological testing surged. In this study, we showed very strong positive correlation between venous blood collection and Mitra home sampling kits for the detection of anti- spike IgGs using an in-house ELISA protocol (based on a protocol from Mt. Sinai). This study demonstrates the utility of using at-home, patient-centric testing to enhance the sero-surveillance methods currently in place for viral tracking and monitoring.

Blimp1 And Nr4a3 Transcription Factors Reciprocally Regulate Antitumor Car T-Cell Stemness And Exhaustion, Inyoung Jung

Publicly Accessible Penn Dissertations

Chimeric antigen receptor (CAR) T-cells have not induced meaningful clinical responses in solid tumor indications. Loss of T-cell stemness, poor expansion capacity and exhaustion during prolonged tumor antigen exposure are major causes of CAR T-cell therapeutic resistance. scRNA-sequencing analysis of CAR T-cells from a first-in-human trial in metastatic prostate cancer identified two distinct and independently validated cell states associated with antitumor potency or lack of efficacy. Low levels of the PRDM1 gene encoding the BLIMP1 transcription factor defined highly potent TCF7+CD8+ CAR T-cells, while enrichment of TIM3+CD8+ T-cells with elevated PRDM1 expression predicted poor outcome. PRDM1 single knockout promoted TCF7-dependent …

Rapid, Site-Specific Labeling Of 'Off-The-Shelf' And Native Serum Autoantibodies With T Cell-Redirecting Domains, Fabiana Zappala

Publicly Accessible Penn Dissertations

Generating new bispecific antibodies typically requires extensive engineering and cloning. New technologies such as made-to-order genes, advanced expression systems, and high efficiency cloning have simplified and accelerated this process. However, the timeline to create new bispecific antibodies is in the order of months, the resulting yield can be low, and adequate functionality is not guaranteed.Here, we developed a simple method to produce bispecific antibodies by site-specifically and covalently attaching a T cell redirecting domain to any off-the-shelf, human Immunoglobulin G (IgG). Our method excludes antibody engineering, cloning or prior knowledge of the antibody sequence, and the bispecifics are created in …

A Serological Analysis Of Sars-Cov-2 Infection In The Obstetric Population, Sophia Rose

CMC Senior Theses

In December 2019, the surfacing and spread of a novel coronavirus, SARS-CoV-2, resulted in the global COVID-19 pandemic. As a viral antigen, SARS-CoV-2 poses a particular threat to the obstetric population due to physiological and immunological changes that women face during pregnancy. While recent studies have found that SARS-CoV-2 may have better clinical outcomes as compared to other betacoronaviruses, adverse pregnancy events such as ICU admission, preeclampsia, and/or preterm birth have been associated with COVID-19. Progress has been made in better understanding the pathophysiology of SARS-CoV-2 in pregnancy, but there is still much to be known about the interaction …

Expanding Mouse-Adapted Yamagata-Like Influenza B Viruses In Eggs Enhances In Vivo Lethality In Balb/C Mice, Matthew J. Pekarek, Erika M. Petro-Turnquist, Adam Rubrum, Richard J. Webby, Eric A. Weaver

Virology Papers

Despite the yearly global impact of influenza B viruses (IBVs), limited host range has been a hurdle to developing a readily accessible small animal disease model for vaccine studies. Mouseadapting IBV can produce highly pathogenic viruses through serial lung passaging in mice. Previous studies have highlighted amino acid changes throughout the viral genome correlating with increased pathogenicity, but no consensus mutations have been determined. We aimed to show that growth system can play a role in mouse-adapted IBV lethality. Two Yamagata-lineage IBVs were serially passaged 10 times in mouse lungs before expansion in embryonated eggs or Madin–Darby canine kidney cells …

Immunogenicity And Protective Efficacy Of A Recombinant Pichinde Viral-Vectored Vaccine Expressing Influenza Virus Hemagglutinin Antigen In Pigs, Sushmita Kumari, Jayeshbhai Chaudhari, Qinfeng Huang, Phillip Gauger, Marcelo Nunes De Almeida, Yuying Liang, Hinh Ly, Hiep Vu

Virology Papers

Influenza A virus of swine (IAV-S) is an economically important swine pathogen. The IAV-S hemagglutinin (HA) surface protein is the main target for vaccine development. In this study, we evaluated the feasibility of using the recombinant tri-segmented Pichinde virus (rPICV) as a viral vector to deliver HA antigen to protect pigs against IAV-S challenge. Four groups of weaned pigs (T01–T04) were included in the study. T01 was injected with PBS to serve as a non-vaccinated control. T02 was inoculated with rPICV expressing green fluorescence protein (rPICV-GFP). T03 was vaccinated with rPICV expressing the HA antigen of the IAV-S H3N2 strain …

Determinants Of Virus Variation, Evolution, And Host Adaptation, Katherine Latourrette, Hernan Garcia-Ruiz

Virology Papers

Virus evolution is the change in the genetic structure of a viral population over time and results in the emergence of new viral variants, strains, and species with novel biological properties, including adaptation to new hosts. There are host, vector, environmental, and viral factors that contribute to virus evolution. To achieve or fine tune compatibility and successfully establish infection, viruses adapt to a particular host species or to a group of species. However, some viruses are better able to adapt to diverse hosts, vectors, and environments. Viruses generate genetic diversity through mutation, reassortment, and recombination. Plant viruses are exposed to …

Adenoviral-Vectored Centralized Consensus Hemagglutinin Vaccine Provides Broad Protection Against H2 Influenza A Virus, Erika M. Petro-Turnquist, Brianna L. Bullard, Matthew J. Pekarek, Eric A. Weaver

Virology Papers

Several influenza pandemics have occurred in the past century, one of which emerged in 1957 from a zoonotic transmission of H2N2 from an avian reservoir into humans. This pandemic caused 2–4 million deaths and circulated until 1968. Since the disappearance of H2N2 from human populations, there has been waning immunity against H2, and this subtype is not currently incorporated into seasonal vaccines. However, H2 influenza remains a pandemic threat due to consistent circulation in avian reservoirs. Here, we describe a method of pandemic preparedness by creating an adenoviral-vectored centralized consensus vaccine design against human H2 influenza. We also assessed the …

The Application Of The Skin Virome For Human Identification, Ema H. Graham, Jennifer Clarke, Samodha Fernando, Joshua Herr, Michael Adamowicz

Virology Papers

The use of skin virome offers a unique approach for human identification purposes in instances where a viable and statistically relevant human DNA profile is unavailable. The skin virome may act as an alternative DNA profile and/or an additional form of probative genetic material. To date, no study has attempted to investigate the human virome over a time series across various physical locations of the body to identify its diagnostic potential as a tool for human identification. For this study, we set out to evaluate the stability, diversity, and individualization of the human skin virome. An additional goal was to …

Inhibition Of Bruton Tyrosine Kinase Reduces Neuroimmune Cascade And Promotes Recovery After Spinal Cord Injury, Chen Guang Yu, Vimala Bondada, Hina Iqbal, Kate L. Moore, John C. Gensel, Subbarao Bondada, James W. Geddes

Physiology Faculty Publications

Microglia/astrocyte and B cell neuroimmune responses are major contributors to the neurological deficits after traumatic spinal cord injury (SCI). Bruton tyrosine kinase (BTK) activation mechanistically links these neuroimmune mechanisms. Our objective is to use Ibrutinib, an FDA-approved BTK inhibitor, to inhibit the neuroimmune cascade thereby improving locomotor recovery after SCI. Rat models of contusive SCI, Western blot, immunofluorescence staining imaging, flow cytometry analysis, histological staining, and behavioral assessment were used to evaluate BTK activity, neuroimmune cascades, and functional outcomes. Both BTK expression and phosphorylation were increased at the lesion site at 2, 7, 14, and 28 days after SCI. Ibrutinib …