Medicine and Health Sciences Commons^™

Saponin Tql1055 Adjuvant-Containing Vaccine Confers Protection Upon Mycobacterium Tuberculosis Challenge In Mice, Mushtaq Ahmed, Eric Farris, Rosemary V Swanson, Shibali Das, Yan Yang, Tyler Martin, Shabaana A Khader

2020-Current year OA Pubs

Tuberculosis (TB), caused by the intracellular pathogen

The Association Of Caregiver Attitudes, Information Sources, And Trust With Hpv Vaccine Initiation Among Adolescents, Akila Anandarajah, Thembekile Shato, Sarah Humble, Alan R Barnette, Heather M Brandt, Lisa M Klesges, Vetta L Sanders Thompson, Michelle I Silver

2020-Current year OA Pubs

This study described caregiver attitudes and the information sources they access about HPV vaccination for adolescents and determined their influence on human papillomavirus (HPV) vaccination initiation. An online survey was administered to 1,016 adults in July 2021. Participants were eligible if they were the caregiver of a child aged 9-17 residing in Mississippi, Arkansas, Tennessee, Missouri, and select counties in Southern Illinois. Multivariate logistic regression was used to estimate the association of caregiver attitudes and information sources with HPV vaccination. Information from doctors or healthcare providers (87.4%) and internet sources other than social media (31.0%) were the most used sources …

Emergent Microenvironments Of Nucleoli, Matthew R King, Kiersten M Ruff, Rohit V Pappu

2020-Current year OA Pubs

In higher eukaryotes, the nucleolus harbors at least three sub-phases that facilitate multiple functionalities including ribosome biogenesis. The three prominent coexisting sub-phases are the fibrillar center (FC), the dense fibrillar component (DFC), and the granular component (GC). Here, we review recent efforts in profiling sub-phase compositions that shed light on the types of physicochemical properties that emerge from compositional biases and territorial organization of specific types of macromolecules. We highlight roles played by molecular grammars which refers to protein sequence features including the substrate binding domains, the sequence features of intrinsically disordered regions, and the multivalence of these distinct types …

Bone Canonical Wnt Signaling Is Downregulated In Type 2 Diabetes And Associates With Higher Advanced Glycation End-Products (Ages) Content And Reduced Bone Strength, Giulia Leanza, Alec T Beeve, Erica L Scheller, Simon Y Tang, Roberto Civitelli, Nicola Napoli, Et Al.

2020-Current year OA Pubs

Type 2 diabetes (T2D) is associated with higher fracture risk, despite normal or high bone mineral density. We reported that bone formation genes (

Csf Biomarkers Of Immune Activation And Alzheimer's Disease For Predicting Cognitive Impairment Risk In The Elderly, Francis Shue, Rachel Hendrix, Jason Ulrich, Rachel L Henson, William Knight, Chengjie Xiong, Jigyasha Timsina, Yun Ju Sung, Carlos Cruchaga, David M Holtzman, Et Al.

2020-Current year OA Pubs

The immune system substantially influences age-related cognitive decline and Alzheimer's disease (AD) progression, affected by genetic and environmental factors. In a Mayo Clinic Study of Aging cohort, we examined how risk factors like APOE genotype, age, and sex affect inflammatory molecules and AD biomarkers in cerebrospinal fluid (CSF). Among cognitively unimpaired individuals over 65 (

Blocking Senescence And Tolerogenic Function Of Dendritic Cells Induced By Γδ Treg Cells Enhances Tumor-Specific Immunity For Cancer Immunotherapy, Fusheng Si, Xia Liu, Yan Tao, Yuanqin Zhang, Feiya Ma, Eddy C Hsueh, Sidharth V Puram, Guangyong Peng

2020-Current year OA Pubs

BACKGROUND: Regulatory T (Treg) cells are a key component in maintaining the suppressive tumor microenvironment and immune suppression in different types of cancers. A precise understanding of the molecular mechanisms used by Treg cells for immune suppression is critical for the development of effective strategies for cancer immunotherapy.

METHODS: Senescence development and tolerogenic functions of dendritic cells (DCs) induced by breast cancer tumor-derived γδ Treg cells were fully characterized using real-time PCR, flow cytometry, western blot, and functional assays. Loss-of-function strategies with pharmacological inhibitor and/or neutralizing antibody were used to identify the potential molecule(s) and pathway(s) involved in DC senescence …

Subcellular Pathways Through Vglut3-Expressing Mouse Amacrine Cells Provide Locally Tuned Object-Motion-Selective Signals In The Retina, Karl Friedrichsen, Jen-Chun Hsiang, Chin-I Lin, Liam Mccoy, Katia Valkova, Daniel Kerschensteiner, Josh L Morgan

2020-Current year OA Pubs

VGluT3-expressing mouse retinal amacrine cells (VG3s) respond to small-object motion and connect to multiple types of bipolar cells (inputs) and retinal ganglion cells (RGCs, outputs). Because these input and output connections are intermixed on the same dendrites, making sense of VG3 circuitry requires comparing the distribution of synapses across their arbors to the subcellular flow of signals. Here, we combine subcellular calcium imaging and electron microscopic connectomic reconstruction to analyze how VG3s integrate and transmit visual information. VG3s receive inputs from all nearby bipolar cell types but exhibit a strong preference for the fast type 3a bipolar cells. By comparing …

A Compendium Of Multi-Omics Data Illuminating Host Responses To Lethal Human Virus Infections, Amie J Eisfeld, Larissa B Thackray, Qing Tan, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Human infections caused by viral pathogens trigger a complex gamut of host responses that limit disease, resolve infection, generate immunity, and contribute to severe disease or death. Here, we present experimental methods and multi-omics data capture approaches representing the global host response to infection generated from 45 individual experiments involving human viruses from the Orthomyxoviridae, Filoviridae, Flaviviridae, and Coronaviridae families. Analogous experimental designs were implemented across human or mouse host model systems, longitudinal samples were collected over defined time courses, and global multi-omics data (transcriptomics, proteomics, metabolomics, and lipidomics) were acquired by microarray, RNA sequencing, or mass spectrometry analyses. For …

Sensitive Mrd Detection From Lymphatic Fluid After Surgery In Hpv-Associated Oropharyngeal Cancer, Noah Earland, Nicholas P Semenkovich, Ricardo J Ramirez, Peter K Harris, Andrew I Hearn, Matthew Inkman, Jeffrey J Szymanski, Benjamin M Wahle, Kevin Chen, Irfan Alahi, Gabris Ni, Andrew Chen, Jin Zhang, Aadel A Chaudhuri, Et Al.

2020-Current year OA Pubs

PURPOSE: Our goal was to demonstrate that lymphatic drainage fluid (lymph) has improved sensitivity in quantifying postoperative minimal residual disease (MRD) in locally advanced human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) compared with plasma, and leverage this novel biofluid for patient risk stratification.

EXPERIMENTAL DESIGN: We prospectively collected lymph samples from neck drains of 106 patients with HPV (+) OPSCC, along with 67 matched plasma samples, 24 hours after surgery. PCR and next-generation sequencing were used to quantify cancer-associated cell-free HPV (cf-HPV) and tumor-informed variants in lymph and plasma. Next, lymph cf-HPV and variants were compared with TNM stage, …

Reliability And Validity Of Smartphone Cognitive Testing For Frontotemporal Lobar Degeneration, Adam M Staffaroni, Nupur Ghoshal, Jason Hassenstab, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Frontotemporal lobar degeneration (FTLD) is relatively rare, behavioral and motor symptoms increase travel burden, and standard neuropsychological tests are not sensitive to early-stage disease. Remote smartphone-based cognitive assessments could mitigate these barriers to trial recruitment and success, but no such tools are validated for FTLD.

OBJECTIVE: To evaluate the reliability and validity of smartphone-based cognitive measures for remote FTLD evaluations.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study conducted from January 10, 2019, to July 31, 2023, controls and participants with FTLD performed smartphone application (app)-based executive functioning tasks and an associative memory task 3 times over 2 weeks. …

Incidence And Mortality Of Covid-19-Associated Invasive Fungal Infections Among Critically Ill Intubated Patients: A Multicenter Retrospective Cohort Analysis, Julio C Zuniga-Moya, Benjamin Papadopoulos, Armaghan-E-Rehman Mansoor, Patrick B Mazi, Adriana M Rauseo, Andrej Spec

2020-Current year OA Pubs

BACKGROUND: An association between coronavirus disease 2019 (COVID-19)-associated invasive fungal infections (CAIFIs) and high mortality among intubated patients has been suggested in previous research. However, some of the current evidence was derived from small case series and multicenter studies conducted during different waves of the COVID-19 pandemic. We examined the incidence of CAIFIs and their associated mortality using a large, multicenter COVID-19 database built throughout the pandemic.

METHODS: We conducted a retrospective analysis of the National COVID Cohort Collaborative (N3C) database collected from 76 medical centers in the United States between January 2020 and August 2022. Patients were 18 years …

Dna Combing Versus Dna Spreading And The Separation Of Sister Chromatids, Alice Meroni, Sophie E Wells, Carmen Fonseca, Arnab Ray Chaudhuri, Keith W Caldecott, Alessandro Vindigni

2020-Current year OA Pubs

DNA combing and DNA spreading are two central approaches for studying DNA replication fork dynamics genome-wide at single-molecule resolution by distributing labeled genomic DNA on coverslips or slides for immunodetection. Perturbations in DNA replication fork dynamics can differentially affect either leading or lagging strand synthesis, for example, in instances where replication is blocked by a lesion or obstacle on only one of the two strands. Thus, we sought to investigate whether the DNA combing and/or spreading approaches are suitable for resolving adjacent sister chromatids during DNA replication, thereby enabling the detection of DNA replication dynamics within individual nascent strands. To …

Cognitive Flexibility Training For Chronic Pain: A Randomized Clinical Study, Katherine J. Holzer, Marko S. Todorovic, Elizabeth A. Wilson, Aaron Steinberg, Michael S. Avidan, Simon Haroutounian

2020-Current year OA Pubs

INTRODUCTION: Previous studies suggest an association between cognitive flexibility and development of chronic pain after surgery. It is not known whether cognitive flexibility can be improved in patients with chronic pain.

OBJECTIVES: This study tested whether a neurocognitive training program results in improved cognitive flexibility and pain in patients with chronic pain.

METHODS: We conducted a single-center, prospective, randomized study investigating 5-week daily neurocognitive training in patients with chronic pain. Participants (n = 145) were randomized into neurocognitive training or care as usual, and they completed assessments at baseline, posttreatment, and 3 months. The treatment group was asked to spend …

Prevotella Copri And Microbiota Members Mediate The Beneficial Effects Of A Therapeutic Food For Malnutrition, Hao-Wei Chang, Evan M Lee, Yi Wang, Cyrus Zhou, Kali M Pruss, Suzanne Henrissat, Robert Y Chen, Clara Kao, Matthew C Hibberd, Hannah M Lynn, Daniel M Webber, Marie Crane, Jiye Cheng, Ye Chen, Jeffrey I Gordon, Et Al.

2020-Current year OA Pubs

Microbiota-directed complementary food (MDCF) formulations have been designed to repair the gut communities of malnourished children. A randomized controlled trial demonstrated that one formulation, MDCF-2, improved weight gain in malnourished Bangladeshi children compared to a more calorically dense standard nutritional intervention. Metagenome-assembled genomes from study participants revealed a correlation between ponderal growth and expression of MDCF-2 glycan utilization pathways by Prevotella copri strains. To test this correlation, here we use gnotobiotic mice colonized with defined consortia of age- and ponderal growth-associated gut bacterial strains, with or without P. copri isolates closely matching the metagenome-assembled genomes. Combining gut metagenomics and metatranscriptomics …

Severity Of Respiratory Syncytial Virus Vs Covid-19 And Influenza Among Hospitalized Us Adults, Diya Surie, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

IMPORTANCE: On June 21, 2023, the Centers for Disease Control and Prevention recommended the first respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older using shared clinical decision-making. Understanding the severity of RSV disease in adults can help guide this clinical decision-making.

OBJECTIVE: To describe disease severity among adults hospitalized with RSV and compare it with the severity of COVID-19 and influenza disease by vaccination status.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, adults aged 18 years and older admitted to the hospital with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively …

Exploring The Association Between Weight Loss-Inducing Medications And Multiple Sclerosis: Insights From The Fda Adverse Event Reporting System Database, Afsaneh Shirani, Anne H Cross, Olaf Stuve

2020-Current year OA Pubs

BACKGROUND: Several studies have demonstrated that early childhood and adolescent obesity are risk factors for multiple sclerosis (MS) susceptibility. Obesity is thought to share inflammatory components with MS through overproduction of pro-inflammatory adipokines (e.g., leptin) and reduction of anti-inflammatory adipokines (e.g, adiponectin). Recently, drug repurposing (i.e. identifying new indications for existing drugs) has garnered significant attention. The US Food and Drug Administration Adverse Event Reporting System (FAERS) database serves not only as a resource for mining adverse drug reactions and safety signals but also for identifying inverse associations and potential medication repurposing opportunities.

OBJECTIVE: We aimed to explore the association …

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society Expert Consensus Statement On Catheter And Surgical Ablation Of Atrial Fibrillation, Stylianos Tzeis, Ralph J Damiano, Et Al.

2020-Current year OA Pubs

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a …

Arch: Improving The Performance Of Clonal Hematopoiesis Variant Calling And Interpretation, Irenaeus C C Chan, Alex Panchot, Evelyn Schmidt, Brian J Wiley, Jie Liu, Kimberly Turner, Duc Tran, J Scott Beeler, Armel Landry Batchi-Bouyou, Daniel C Link, Kelly L Bolton, Et Al.

2020-Current year OA Pubs

MOTIVATION: The acquisition of somatic mutations in hematopoietic stem and progenitor stem cells with resultant clonal expansion, termed clonal hematopoiesis (CH), is associated with increased risk of hematologic malignancies and other adverse outcomes. CH is generally present at low allelic fractions, but clonal expansion and acquisition of additional mutations leads to hematologic cancers in a small proportion of individuals. With high depth and high sensitivity sequencing, CH can be detected in most adults and its clonal trajectory mapped over time. However, accurate CH variant calling is challenging due to the difficulty in distinguishing low frequency CH mutations from sequencing artifacts. …

Structure Of Alpha-Synuclein Fibrils Derived From Human Lewy Body Dementia Tissue, Dhruva D Dhavale, Katherine Basore, Isabelle R Gordon, Jialu Liu, Jennifer Y O'Shea, Michael J Rau, Zachary Smith, Brock Summers, Richard J Perrin, Joel S Perlmutter, James A J Fitzpatrick, Paul T Kotzbauer, Et Al.

2020-Current year OA Pubs

The defining feature of Parkinson disease (PD) and Lewy body dementia (LBD) is the accumulation of alpha-synuclein (Asyn) fibrils in Lewy bodies and Lewy neurites. Here we develop and validate a method to amplify Asyn fibrils extracted from LBD postmortem tissue samples and use solid state nuclear magnetic resonance (SSNMR) studies to determine atomic resolution structure. Amplified LBD Asyn fibrils comprise a mixture of single protofilament and two protofilament fibrils with very low twist. The protofilament fold is highly similar to the fold determined by a recent cryo-electron microscopy study for a minority population of twisted single protofilament fibrils extracted …

Comparative Lipidome Study Of Maternal Plasma, Milk, And Lamb Plasma In Sheep, Soundara Viveka Thangaraj, Adel Ghnenis, Brooke Pallas, Arpita Kalla Vyas, Brigid Gregg, Vasantha Padmanabhan

2020-Current year OA Pubs

Lipids play a critical role in neonate development and breastmilk is the newborn's major source of lipids. Milk lipids directly influence the neonate plasma lipid profile. The milk lipidome is dynamic, influenced by maternal factors and related to the maternal plasma lipidome. The close inter-relationship between the maternal plasma, milk and neonate plasma lipidomes is critical to understanding maternal-child health and nutrition. In this exploratory study, lipidomes of blood and breast milk from Suffolk sheep and matched lamb blood (n = 13), were profiled on day 34 post birth by untargeted mass spectrometry. Comparative multivariate analysis of the three matrices …

Fibrinolytic-Deficiencies Predispose Hosts To Septicemia From A Catheter-Associated Uti, Jonathan J Molina, Wei Xu, Karla Bergeron, Aleksandra Klim, Michael G Caparon, Scott J Hultgren, Alana Desai, Et Al.

2020-Current year OA Pubs

Catheter-associated urinary tract infections (CAUTIs) are amongst the most common nosocomial infections worldwide and are difficult to treat partly due to development of multidrug-resistance from CAUTI-related pathogens. Importantly, CAUTI often leads to secondary bloodstream infections and death. A major challenge is to predict when patients will develop CAUTIs and which populations are at-risk for bloodstream infections. Catheter-induced inflammation promotes fibrinogen (Fg) and fibrin accumulation in the bladder which are exploited as a biofilm formation platform by CAUTI pathogens. Using our established mouse model of CAUTI, here we identified that host populations exhibiting either genetic or acquired fibrinolytic-deficiencies, inducing fibrin deposition …

Next Generation Microfluidics: Fulfilling The Promise Of Lab-On-A-Chip Technologies, Umut A Gurkan, Jorge Di Paola, Et Al.

2020-Current year OA Pubs

Microfluidic lab-on-a-chip technologies enable the analysis and manipulation of small fluid volumes and particles at small scales and the control of fluid flow and transport processes at the microscale, leading to the development of new methods to address a broad range of scientific and medical challenges. Microfluidic and lab-on-a-chip technologies have made a noteworthy impact in basic, preclinical, and clinical research, especially in hematology and vascular biology due to the inherent ability of microfluidics to mimic physiologic flow conditions in blood vessels and capillaries. With the potential to significantly impact translational research and clinical diagnostics, technical issues and incentive mismatches …

Impact Of Imaging Frequency On Progression-Free Survival In Alliance Trials Enrolling Patients With Follicular Lymphoma, Sarah C Rutherford, Jun Yin, Levi D Pederson, Kristie A Blum, Peter Martin, Sin-Ho Jung, Barbara Grant, Cara Rosenbaum, Bruce D Cheson, Nancy L Bartlett, Sumithra J Mandrekar, John P Leonard

2020-Current year OA Pubs

No abstract provided.

Phase 2 Study Of Add-On Parsaclisib For Patients With Myelofibrosis And Suboptimal Response To Ruxolitinib: Final Results, Abdulraheem Yacoub, Stephen T Oh, Et Al.

2020-Current year OA Pubs

Ruxolitinib reduces spleen volume, improves symptoms, and increases survival in patients with intermediate- or high-risk myelofibrosis. However, suboptimal response may occur, potentially because of signaling via the phosphoinositide 3-kinase (PI3K)/protein kinase B pathway. This phase 2 study evaluated dosing, efficacy, and safety of add-on PI3Kδ inhibitor parsaclisib for patients with primary or secondary myelofibrosis with suboptimal response to ruxolitinib. Eligible patients remained on a stable ruxolitinib dose and received add-on parsaclisib 10 or 20 mg, once daily for 8 weeks, and once weekly thereafter (daily-to-weekly dosing; n = 32); or parsaclisib 5 or 20 mg, once daily for 8 weeks, …

Targeting Cxcr4, Vla-4, And Cxcr2 For Hematopoietic Stem Cell Mobilization, Daniel Cancilla, Michael P Rettig, Darja Karpova, Haresh Thakellapalli, Megh Singh, Marvin J Meyers, Peter G Ruminski, Stephanie Christ, Ezhilarasi Chendamarai, Feng Gao, Leah Gehrs, Julie K Ritchey, Michael Prinsen, John F Dipersio

2020-Current year OA Pubs

No abstract provided.

Intergenerational Protective Anti-Gut Commensal Immunoglobulin G Originates In Early Life, Brigida Rusconi, Adina K Bard, Ryan Mcdonough, Angel M Kindsvogel, Jacqueline D Wang, Sreeram Udayan, Keely G Mcdonald, Rodney D Newberry, Phillip I Tarr

2020-Current year OA Pubs

Maternal immunoglobulins of the class G (IgGs) protect offspring from enteric infection, but when, where, and how these antibodies are physiologically generated and confer protection remains enigmatic. We found that circulating IgGs in adult mice preferentially bind early-life gut commensal bacteria over their own adult gut commensal bacteria. IgG-secreting plasma cells specific for early-life gut bacteria appear in the intestine soon after weaning, where they remain into adulthood. Manipulating exposure to gut bacteria or plasma cell development before, but not after, weaning reduced IgG-secreting plasma cells targeting early-life gut bacteria throughout life. Further, the development of this anti-gut commensal IgG …

The Disordered N-Terminal Tail Of Sars-Cov-2 Nucleocapsid Protein Forms A Dynamic Complex With Rna, Jasmine Cubuk, Jhullian J Alston, J Jeremías Incicco, Alex S Holehouse, Kathleen B Hall, Melissa D Stuchell-Brereton, Andrea Soranno

2020-Current year OA Pubs

The SARS-CoV-2 Nucleocapsid (N) protein is responsible for condensation of the viral genome. Characterizing the mechanisms controlling nucleic acid binding is a key step in understanding how condensation is realized. Here, we focus on the role of the RNA binding domain (RBD) and its flanking disordered N-terminal domain (NTD) tail, using single-molecule Förster Resonance Energy Transfer and coarse-grained simulations. We quantified contact site size and binding affinity for nucleic acids and concomitant conformational changes occurring in the disordered region. We found that the disordered NTD increases the affinity of the RBD for RNA by about 50-fold. Binding of both nonspecific …

Pathogenic Variants In Crx Have Distinct Cis-Regulatory Effects On Enhancers And Silencers In Photoreceptors, James L Shepherdson, Ryan Z Friedman, Yiqiao Zheng, Chi Sun, Inez Y Oh, David M Granas, Barak A Cohen, Shiming Chen, Michael A White

2020-Current year OA Pubs

Dozens of variants in the gene for the homeodomain transcription factor (TF) cone-rod homeobox (

Combined Kras-Mapk Pathway Inhibitors And Her2-Directed Drug Conjugate Is Efficacious In Pancreatic Cancer, Ashenafi Bulle, Peng Liu, Kuljeet Seehra, Sapana Bansod, Yali Chen, Kiran Zahra, Vikas Somani, Iftikhar Ali Khawar, Hung-Po Chen, Paarth B Dodhiawala, Lin Li, Yutong Geng, Chia-Kuei Mo, Jay Mahsl, Li Ding, Ramaswamy Govindan, Sherri Davies, Jacqueline Mudd, William G Hawkins, Ryan C Fields, David G Denardo, Jason M Held, Patrick M Grierson, Andrea Wang-Gillam, Marianna B Ruzinova, Kian-Huat Lim, Et Al.

2020-Current year OA Pubs

Targeting the mitogen-activated protein kinase (MAPK) cascade in pancreatic ductal adenocarcinoma (PDAC) remains clinically unsuccessful. We aim to develop a MAPK inhibitor-based therapeutic combination with strong preclinical efficacy. Utilizing a reverse-phase protein array, we observe rapid phospho-activation of human epidermal growth factor receptor 2 (HER2) in PDAC cells upon pharmacological MAPK inhibition. Mechanistically, MAPK inhibitors lead to swift proteasomal degradation of dual-specificity phosphatase 6 (DUSP6). The carboxy terminus of HER2, containing a TEY motif also present in extracellular signal-regulated kinase 1/2 (ERK1/2), facilitates binding with DUSP6, enhancing its phosphatase activity to dephosphorylate HER2. In the presence of MAPK inhibitors, DUSP6 …

Epitope Mapping Of Japanese Encephalitis Virus Neutralizing Antibodies By Native Mass Spectrometry And Hydrogen/Deuterium Exchange, Jagat Adhikari, James Heffernan, Melissa Edeling, Estefania Fernandez, Prashant N Jethva, Michael S Diamond, Daved H Fremont, Michael L Gross

2020-Current year OA Pubs

Japanese encephalitis virus (JEV) remains a global public health concern due to its epidemiological distribution and the existence of multiple strains. Neutralizing antibodies against this infection have shown efficacy in in vivo studies. Thus, elucidation of the epitopes of neutralizing antibodies can aid in the design and development of effective vaccines against different strains of JEV. Here, we describe a combination of native mass spectrometry (native-MS) and hydrogen/deuterium exchange mass spectrometry (HDX-MS) to complete screening of eight mouse monoclonal antibodies (MAbs) against JEV E-DIII to identify epitope regions. Native-MS was used as a first pass to identify the antibodies that …