Chemicals and Drugs Commons^™

Phytochemical And In-Vitro Cytotoxic Analyses Of Flavonoid Species Isolated From Chromolaena Leivensis, Luke A. Bryant

Electronic Theses and Dissertations

As a leading cause of death worldwide, cancer and its treatments remain a primary source of interest among researchers. Modern studies are looking into bioselective cytotoxicity to create new chemotherapies that do not have the same harsh side effects as those we use today. Natural product research has a promising future for the development of such treatments. Specifically, polar flavonoids may be the key to a bioselective treatment. Such flavonoid species are native to plants, often within flower petals or within the body. A natural antioxidant, they are designed not to harm healthy cells. This study focuses on the plant …

Overview Of Glp-1ra Medications, Thomas A.F. Cordaro Pharmd, Sumaiya A. Difaa Pharmd, Amel J. Basil Pharmd

Transformative Medicine

GLP-1 is an incretin hormone that is naturally produced in the body that regulates blood glucose and appetite. The first GLP-1RA that was FDA approved, exenatide, in 2005, originated from the Gila monster and beaded lizard, via the discovery of the exendin-4 peptide. GLP-1RAs function by mimicking endogenous GLP-1 incretin hormone, leading to an increase in glucose-dependent insulin release from beta-cells of the pancreas, decrease in glucagon release, delayed gastric emptying, and satiety. Due to the benefits seen from initiating GLP-1RAs in the market, it sparked interest in numerous studies which proved that certain GLP-1RAs can provide cardiorenal protection. The …

Glp-1 Receptor Agonists And Wound Healing In Diabetic Foot Ulcers: A Scoping Review, Merlin Sajeev, Amanda L. Killeen

School of Podiatric Medicine - Student Research

Level of Evidence: Level 5

Poster Category: Non-sponsored

Introduction: Diabetic foot ulcers (DFUs) are a major complication of diabetes and are associated with delayed wound healing, infection, amputation, and substantial morbidity. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve glycemic control and may influence inflammation, vascular function, and tissue repair. However, clinical evidence evaluating their relationship with DFU healing remains limited.

Aim: To characterize available clinical evidence examining the association between GLP-1 RA use and wound-healing outcomes in patients with diabetic foot ulcers.

Methods: PubMed and Google Scholar were searched for English-language studies published from 2021–2026 using terms combining “GLP-1 receptor …

Charge Modulation Of Peptide/Nucleic Acid Complexes: An Anionic Additive Enhances Gene Silencing And Crispr/Cas9 Editing By Promoting Intracellular Nucleic Acid Release, Abdulelah Alhazza, Sorour Khayyatnejad Shoushtari, Hasan Uludag, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Introduction: Small interfering RNA (siRNA) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated Protein 9 (Cas9) complexes are effective approaches to temporarily downregulate protein expression via post-transcription RNA interference or permanently altering protein expression via editing genomic DNA, respectively. However, the efficient delivery of these mediators to targeted cells has been challenging, largely due to their anionic and hydrophilic nature, which hinders their interaction with the cell membrane and cellular internalization. Cell-penetrating peptides (CPPs) exhibit dual characteristics as a carrier for nucleic acid delivery, where positively charged components bind to the negatively charged nucleic acid, and the hydrophobic components …

Quality Improvement Initiative To Improve Adherence To Ob Hemorrhage Policy And Standardize Pitocin Administration During Cesarean Sections To Reduce Postpartum Hemorrhage Risk, Lauren R. Litz, Monica Blauser

Doctor of Nurse Anesthesia Practice (DNAP) Manuscripts

Postpartum hemorrhage remains a leading cause of maternal morbidity and mortality, and Pitocin administration is an important component of hemorrhage prevention and management during cesarean delivery. Variation in Pitocin timing, dosing, method of administration, and adherence to evidence-based recommendations may compromise patient safety and create barriers to standardized obstetric anesthesia care. The purpose of this Doctorate of Nurse Anesthesia Practice quality improvement project was to evaluate current anesthesia provider practices for Pitocin administration during cesarean delivery, compare observed practices with the California Maternal Quality Care Collaborative hemorrhage toolkit and Society for Obstetric Anesthesia and Perinatology Enhanced Recovery After Cesarean recommendations, …

Calcium Signaling And Postsynaptic Density Dynamics: The Roles Of Calmodulin In Synaptic Protein Regulation, Keyaa Dilip Shah, Yonghong Zhang

School of Integrative Biological & Chemical Sciences Faculty Publications

Calcium signaling in neuronal cells is the principal mechanism underlying learning and synaptic plasticity, whereas the postsynaptic density (PSD) is an important center where calcium-dependent processes are organized and regulated. This review explores the roles of calmodulin (CaM) in facilitating calcium-dependent modulation of the activities of synaptic proteins in the PSD. We focus on the molecular processes through which CaM interacts with calcium signals to regulate the function, localization, and interactions of central synaptic proteins, including calcium/calmodulin-dependent protein kinase II (CaMKII), membrane-associated guanylate kinases (MAGUKs), and N-methyl-D-aspartate (NMDA) receptors. We aim to summarize recent advances in structural, biochemical, and imaging …

Evaluating The Market Withdrawal Of Andexanet Alfa, Jordyn Linfield, Addisyn Cooper, Alexander Defranco, Emma Gerding, Jessica Kelley, Tyler Henney, Connor Dains, Brenna Hissong, Brittany Bates

Pharmacy and Wellness Review

The coagulation cascade comprises intrinsic, extrinsic, and common pathways that converge when thrombin converts fibrinogen (factor I) into fibrin, leading to fibrin mesh formation, stabilization of the platelet plug, and ultimately thrombus formation. Inhibition of the coagulation cascade can be achieved with a variety of anticoagulant medications, including direct oral anticoagulants (DOACs). The mechanism of action of DOACs is to inhibit either factor Xa or thrombin. Reversal of anticoagulation remains an important clinical consideration when managing patients on DOACs who experience serious bleeding events. Andexanet alfa is a recombinant, modified human factor Xa protein previously indicated for patients receiving rivaroxaban …

Accelerating Wound Healing Rates With Cucurbita Pepo Leaf Extract Loaded Electrospun Poly(Methyl Methacrylate)/Halloysite/Chitosan/ Caco₃ Composite Nanofibers Through In Vitro And In Vivo Assessments, Samar A. Salim

Nanotechnology Research Centre

Cucurbita pepo leaf extract (CPE) was incorporated into electrospun poly(methyl methacrylate)/ halloysite/chitosan/ CaCO₃ (PMMA/Hal/CS/CaCO₃) composite nanofibers to develop a novel biomaterial for accelerating wound healing rates. The different nanofibrous scaffolds were successfully fabricated and characterized through scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). SEM analysis revealed uniform, smooth nanofibers, while FTIR and XRD confirmed the integration of CPE into nanofiber matrix, indicating an amorphous structure and effective dispersion of the extract. In vitro agar well-diffusion and antibiofilm assays revealed that the optimized formulation exhibited potent antimicrobial activity against wound-associated pathogens. The nanofibers composite based on …

Health Practices And Use Of Traditional Medicine Among Asian Indian Immigrants In The United States: A Pilot Study, Parita Patel, Anil N.F. Aranha

Medical Student Research Symposium

Title: Health Practices and Use of Traditional Medicine Among Asian Indian Immigrants in the United States: A Pilot Study

Authors

Parita Patel, MPH¹; Anil N.F. Aranha, PhD^1,2

Medical Education¹, Internal Medicine², Wayne State University School of Medicine, Detroit, Michigan

Abstract

Background and Purpose: Traditional and alternative medicine (TAM), including Ayurveda, Homeopathy, Naturopathy, and home remedies, remains widely used among Asian Indian (AI) immigrants in the United States alongside Western medicine. Cultural familiarity, family influence, and perceived safety shape these practices. This pilot study examined TAM prevalence, patterns, and perceptions among AI immigrants and …

Quality Improvement (Qi) Project Aimed At Reducing Unnecessary Antibiotic Usage Among Older Adult Patients By Addressing Inappropriate Antibiotic Prescribing In Primary And Long-Term Care Settings, Pamela M. Thomas

Seton Hall University Dissertations and Theses (ETDs)

Antibiotic overuse among older adults remains a significant patient safety and public health concern. Recent national data indicate that approximately 30%–50% of outpatient antibiotic prescriptions may be unnecessary, particularly for viral or self-limiting conditions (Chua et al., 2021). Antimicrobial resistance has been associated with more than 1.27 million deaths globally (Murray et al., 2022). This quality improvement project evaluated a multifaceted antimicrobial stewardship intervention in primary and long-term care settings. Baseline review of 167 antibiotic cases revealed 37.1% were inappropriate or questionable, and 28.7% lacked adequate diagnostic documentation. The intervention incorporated provider education, electronic health record decision-support tools, audit and …

Developing Antibodies Against Galectin-3 And Galectin-9 To Target Endometriosis, Ashleigh Burger, Noah Farnsworth, Jared J. Reisnouer, Cheyenne Vue

2026 Symposium

Endometriosis is a disease characterized by pelvic pain and the formation of endometrial-like tissue on the outside of the uterine lining. This condition affects nearly 10% of women across the globe and confirming whether someone has endometriosis requires visualization in surgery. While the specific causes of this disease remain unclear, the over-expression of the Galectins 3 and 9 in ectopic endometrial tissues suggests a role in the development and maintenance of the condition. Monoclonal antibodies (mAbs) are highly specific proteins with potential as diagnostic or treatment tools. The goal of this study is to generate antibodies against Gal3 and Gal9. …

Quantifying Black Carbon Concentrations In Georgia And Analyzing Associated Public Health Risks, Khloe R. Osborne

Honors Theses

Quantifying Black Carbon Concentrations in Georgia and Analyzing Associated Public Health Risks

One of the most daunting challenges of the industrial world is air pollution. Within this broad spectrum, there is an inhalable particle group named PM2.5, which contains black carbon. Black carbon has evidence that supports the generation and worsening of adverse health impacts, which may include birth complications, cognitive deficits in children, pulmonary aggravation, asthma, cardiovascular issues, neurological degenerative patterns, and cancer risk. This is especially seen in vulnerable populations, like children, elderly, and those who already suffer from weakened health, many of which reside in the southern …

Anticholinergic Toxicity Presenting As Acute Stroke Mimic: A Case Report, Dean Austin Esma, Kelsey Murray, James Espinosa, Alan Lucerna

Rowan-Virtua Research Day

Anticholinergic toxicity classically presents with a constellation of peripheral and central symptoms including tachycardia, mydriasis, dry skin, urinary retention, and altered mental status. However, central anticholinergic effects can predominate, presenting as isolated delirium without peripheral manifestations. This report presents a case of a 57-year-old woman who developed acute altered mental status and aphasia following cumulative anticholinergic exposure from over-the-counter cold medications, initially triggering a stroke alert

Sex Differences In Insulin Resistance And Triglyceride/Hdl-Cholesterol Ratio In Human Subjects, Jiyoon Jung, Lakshman Segar, Christine Whitehair, James Bailey, Ashley Coleman, George Scott

Rowan-Virtua Research Day

Background: Insulin resistance (IR) plays a major role in dyslipidemia and the associated cardiovascular disease risk. To date, it remains unclear as to how IR alters plasma lipid profile in males versus females. The present study is an initial step to determine sex-specific differences in IR and plasma lipid profile using 40 μL of capillary blood. Methods: 19 adults aged 30-64 were recruited from Rowan Medicine-Sewell clinics, with 13 participants (9 males, 4 females) consenting to the study. After collecting 40 μL of capillary blood via finger prick, the samples were analyzed for glucose, triglyceride (TG), and HDL-cholesterol (HDL-C) using …

Ai×Life 2026: Advances In Computational Biology Across Scales For Life & Health Sciences, Suma Mohan S., Devika N. T., Pranavathiyani G.

Conference Proceedings

Book of Abstracts of the International Conference, AIxLife 2026: Advances in Computational Biology Across Scales for Life & Health Sciences, held on 17–18 April 2026, SASTRA Deemed to be University, Thanjavur, Tamil Nadu, INDIA 

About the Conference

Conventional computational biology laid the foundation for biological data analysis through statistical models, algorithms, and curated databases, enabling insights into genes, proteins, and pathways. Today, the integration of artificial intelligence, spanning machine learning, deep learning, and large language models (LLMs) is driving a transformative shift across biological scales, from atomic and molecular interactions to pathways, cellular systems, organisms, and populations.

AI-powered approaches …

The Impact Of Glucose Exposure On Organic Cation Transporters (Oct) Function In A Corneal Epithelial Cell Line, David A. Garza

Theses & Dissertations

Organic cation transporters (OCT) facilitate the movement of neurochemicals and medications, contribute to the removal of cellular waste, and facilitate neuronal communication. Three subtypes of these high-capacity, low-affinity transporters (OCT1, OCT2, and OCT3) are differently expressed in peripheral tissues such as the liver, kidneys, as well as the central nervous system. OCTs are also expressed in ocular tissues. Chronic hyperglycemia is a complication commonly associated with diabetes that can lead to ocular diseases such as diabetic keratopathy, which affects the cornea. In this project, we expose immortalized human corneal epithelial cells (HCE-S) to various glucose concentrations to study their impact …

Methionine Restriction Enhances Platinum-Based Chemotherapy-Induced Immunogenic Cell Death In Triple Negative Breast Cancer Cells, Mallory Thompson, Laura Sipe Ph.D.

Departmental Honors & Graduate Capstone Projects

When cancer cells are treated with chemotherapy, they can release Damage-Associated Molecular Patterns (DAMPs) as they die that can alert and engage the immune system, a process known as an immunogenic cell death (ICD). The dying cancer cell can release certain molecules, including ATP or calreticulin, that immune cells first recognize as abnormal before initiating an anti-tumor response. However, not all chemotherapies cause the release of these beneficial signals as they kill the cell. This study aims to determine whether a specific deprivation technique, called methionine restriction, enhances the ICD process and DAMP expression when used in conjunction with chemotherapy …

Antibacterial Tellurium Dioxide Nanoparticles Incorporated Into An Adhesive Wound Dressing, Tina Hesabizadeh, Rajendra Subedi, Rolando Baez, Thomas J. Webster, Gregory Guisbiers

Faculty Scholarship

Tellurium dioxide (TeO2) nanoparticles were synthesized by pulsed laser ablation in liquids (PLAL) using a bottom-ablation configuration, with deionized water as the solvent and pure tellurium pellets as the target. The resulting nanoparticles were spherical, with an average diameter of 56 ± 13 nm. Phase analysis indicated that the nanoparticles consisted mainly of around 83% of paratellurite α-TeO2, with a minor fraction, i.e., around 17% of the metastable γ-TeO2 phase. The antibacterial performance of the TeO2 nanoparticles was evaluated against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and methicillin-resistant Staphylococcus aureus (MRSA), demonstrating broad-spectrum antibacterial activity at concentrations as low as …

Exploration Of A Relationship Between The Activities Of Trail And 4’-Trifluoromethoxychalcone., Abigail C. Ernst

Undergraduate Theses

Cancer is the overgrowth of dysregulated or mutated cells that affects 1 in 3 Americans. Chalcones are natural products with many possible derivatives, such as 4’-trifluromethoxychalcone (4TF), developed in Dr. Krzysiak’s lab, which exhibit anticancer activity against cancer cell lines. Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) is a tumor surveillance cytokine that acts on two receptor types: death receptors and decoy receptors. One way cancer cells can become resistant to TRAIL is by upregulating decoy receptors and/or downregulating death receptors. In this study, MTS assays evaluated the potential relationship between TRAIL and 4TF that sensitizes A549 cells to TRAIL. The …

A Ubiquitin Code Written In Circadian Time: Evaluating Protein Linkages In A Drosophila Model, Alejandro Damian, Elinor Harrison, Cj Dalton

Medical Student Research Symposium

Background: Ubiquitin is a small polypeptide that serves many functions within a cell, including modifying proteins, marking them for degradation through the ubiquitin-proteasome system (UPS). Circadian rhythms regulate many cellular processes, but its role on the individual linkages of ubiquitin is poorly understood. This project aims to determine whether there is a circadian pattern for the conjugation of ubiquitin. Methods: Wild-type (Oregon R) Drosophila were entrained to a circadian cycle with standard light and dark environments. The whole heads were then frozen and removed at different times and used to quantify protein linkages using western blotting and antibodies to each …

Folic Acid–Carbon Dot–Gemcitabine Nanoparticles For Targeted Cancer Drug Delivery, Irfan Huda, Hua Mei

SPARK Symposium Presentations

This project aims to develop a folic acid-attached carbon dot nanoparticle system (FA-CDs-GEM) for the targeted delivery of gemcitabine to cancer cells. While gemcitabine is widely used, its effectiveness is limited because a short in vivo half life and lack of selectivity, which lead to severe side effects. Carbon dots offer a simple and modifiable platform as the drug delivery and bioimaging agent. Conjugation of folic acid to the carbon dots enables selective targeting of cancer cells that overexpress folate receptors. In this study, we synthesized and characterized FA-CD-GEM nanoparticles and developed an HPLC calibration curve of GEM to accurately …

The Effects Of Body Mass Index On Fertility And In Vitro Fertilization, Morgan R. Kidd

Honors College Theses

In-vitro fertilization (IVF) is the most widely used type of assisted reproductive technology for treating infertility arising from a number of conditions. As obesity rates continue to climb in the United States, infertility has been discovered to have a direct correlation. Individuals that fall below or above the healthy body mass index range are found to have disrupted regulation of the hypothalamic-pituitary-gonadal axis, resulting in diminished reproductive health. Those that are diagnosed as infertile due to conditions caused by the effects of low body mass index or high body mass index may seek assisted reproductive technologies to intervene in achieving …

Infectious Retinitis Associated With Jak Inhibitors: The Ongoing Duality Of Jak Inhibitors, Jose S. Pulido, Fukutaro Mano, Marcello Casella, Susumu Ishida

Wills Eye Hospital Papers

PURPOSE: To discuss the recent evidence that Janus kinase (JAK) inhibitors can cause viral retinitis.

METHODS: A commentary on the case report in this issue and a review of cases in the literature.

RESULTS: A total of 6 cases have now been reported of cytomegalovirus retinitis associated with Jak inhibitors. Additionally, there was a case of bilateral toxoplasma retinitis and a case of herpetic scleritis.

DISCUSSION: It is important to be aware of the potential blinding complications associated with JAK inhibitors and if the patient complains of acute vision loss and/or floaters, the patient should be emergently referred to a …

A Study Of Awareness Of Antiseptics And Disinfectant Use Among Allied Health Sciences Students And Interns Of A Tertiary Care Hospital, Pooja M, Puneeth A, Sharmi Nm

Digital Journal of Clinical Medicine

Background:

Antiseptics and disinfectants are among the most vital tools in infection prevention and control (IPC), especially in healthcare settings where the risk of hospital-acquired infections (HAIs) remains a significant concern. This study aims to assess the awareness and knowledge of antiseptics and disinfectants among Allied Health Sciences (AHS) students and interns, identify knowledge gaps at different stages of training, and recommend educational interventions.

Methods:

This was a cross-sectional, questionnaire-based study conducted among 1st to 3rd-year AHS students and interns at a tertiary care hospital. Data were collected using a validated questionnaire via a Google form after obtaining approval from …

Relationships Between Clinical Symptom Scales And Eeg Biomarkers In Oud Patients, Jess Delange, Benjamin M. Latey, John Glinski, Braden Ashcraft, Jasmine Pannu, Cassidy Beatty, Lauren Knudson, Benjamin Chafetz, Bryan Fugal, Patrick Tanner Brain, N P. Griffin, Christopher Gowans, Amanda Brandaris, Amanda Page, Blake D. Harris, Sophia Delgado, Lorissa Thorpe, Kyle Bills, Andrew Payne

Annual Research Symposium

This poster examines the relationship between clinical symptom scales and electroencephalographic (EEG) biomarkers in patients with Opioid Use Disorder (OUD). Participants from inpatient substance use treatment facilities completed validated mental health and withdrawal assessments, including the COWS, PHQ-9, HAM-A, and ASRS followed by cognitive testing while undergoing 19-lead EEG recording.

Preliminary findings indicate that synthetic opioid use is associated with prolonged P300 response latency across brain regions, suggesting measurable neurophysiologic differences tied to substance type and addiction severity. The study explores how EEG metrics may complement subjective symptom reporting to provide more objective markers of addiction status, co-morbid psychiatric burden, …

Investigating Tau Pathology In The Retina And Anterior Segment Structures Of The Eye In A 3-Nitropropionic Acid–Induced Tauopathy Mouse Model, Mohamed Sayed Ahmed Abdel-Kader Qasem

Theses and Dissertations

Background and Objectives: Alzheimer's disease, the most prevalent neurodegenerative disorder in older adults, is characterized by accumulation of hyperphosphorylated tau and amyloid-beta (Aβ) plaques in the central nervous system. Given the retina's shared embryological origin with the brain, its direct neural connectivity via the optic nerve, and similarities in vasculature and age-related degeneration patterns, retinal pathology may serve as an early, non-invasive biomarker for Alzheimer's disease. This study employed 3-nitropropionic acid (3NP) as a pathway-specific tauopathy model driven by mitochondrial dysfunction. The study particularly aimed to investigate whether retinal and corneal tau pathology reflects underlying tau-related neurodegeneration triggered by …

Mutations Altering The Dna Binding Domains Of The Human Rad52 Protein Exert Distinct Effects On Homologous Recombination Repair In Saccharomyces Cerevisiae, Glenn M. Manthey, Elise W. Wolf, Jason Xu, M. Cristina Negritto, Renee A. Bouley, Ruben C. Petreaca, Adam M. Bailis

College of Health Professions Faculty Papers

RAD52 is a conserved member of the homologous recombination repair (HRR) apparatus from yeast to humans. Mutating conserved amino acids in the internal and external DNA binding domains of the human RAD52 protein (HsRAD52) has discrete effects in vitro. Previous studies have shown that HsRAD52 supports multiple mechanisms of HRR in budding yeast, suggesting the utility of this model system for exploring the correspondence between losses of HsRAD52 function in vitro and their impact in vivo. We report that disrupting the internal and external DNA binding domains of HsRAD52 produced distinct effects on the repair of genomic DNA double-strand breaks …

Rare Event: Neonatal Anaphylaxis Following Hepatitis B Vaccination – A Case Series From A Tertiary Care Center In India, Aarthi Ma, Revanth R

Advances in Clinical Medical Research and Healthcare Delivery

We report two cases of anaphylaxis following Hepatitis B vaccination in one-day-old neonates at a tertiary care hospital in India. Both cases presented with similar patterns of cutaneous reactions and respiratory symptoms shortly after intramuscular administration of the Hepatitis B vaccine. To our knowledge, this is among the few documented case series of neonatal anaphylaxis post–Hepatitis B vaccination, underscoring its rarity yet clinical importance. The cases highlight the critical importance of vigilant post-vaccination monitoring and prompt recognition of vaccine-associated adverse events in neonates. This report reviews current literature on anaphylaxis following vaccination and discusses optimal management strategies.

Engineering Enac Constructs To Examine Pip2 And Ubiquitin Competition On Enac Regulation And Stability, Lacie Johnson

Chemistry & Biochemistry Undergraduate Honors Theses

The epithelial sodium channel (ENaC) plays a critical role in sodium homeostasis, fluid balance, and blood pressure regulation. ENaC activity is tightly controlled by post-translational mechanisms, including ubiquitination-mediated degradation and phosphatidylinositol 4,5-bisphosphate (PIP2) dependent channel activation. PIP2 is a phospholipid necessary to facilitate the maximal channel opening. Previous studies suggest that intracellular PIP2 binding sites are located in proximity to ubiquitination sites on ENaC subunits, raising the possibility of PIP2 binding to influence channel stability and function. This thesis aimed to engineer and validate molecular tools capable of examining the interplay between PIP2 binding and ubiquitination in ENaC regulation. A …

Optimal Murine Cd4+ T Cell Priming By Mrna-Lipid Nanoparticle Vaccines Requires Endogenous Antigen Processing, Julia E. Rood, Suh Kyung Yoon, Mary K. Heard, Stephen D. Carro, Emma J. Hedgepeth, Mary E. O'Mara, Michael J. Hogan, Nhu Le, Hiromi Muramatsu, Kieu Lam, Petra Schreiner, Coral Kasden, Hansell H. Stedman, Ryan A. Langlois, James Heyes, Norbert Pardi, Laurence C. Eisenlohr

College of Life Sciences Faculty Papers

Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines elicit robust CD4+ T cell responses, yet the mechanisms underlying this T cell priming remain unknown. Antigens presented to CD4+ T cells on major histocompatibility complex class II (MHC II) are traditionally acquired by antigen presenting cells (APCs) from extracellular sources. Here we show that vaccine specific CD4+ T cell responses instead rely on antigen directly expressed within APCs, without extracellular transit. Murine APCs treated with mRNA-LNP vaccines activate T cells more efficiently when presenting antigen produced internally, rather than acquired externally. Immunization with mRNA-LNP vaccines engineered to inhibit antigen expression in APCs results …