Respiratory syncytial virus (RSV) is a major cause of severe respiratory tract disease worldwide, and a pediatric vaccine is not available. We generated a filamentous RSV-based virus-like particle (VLP) that presents the central conserved region of the attachment protein G. This was achieved by co-expressing the matrix protein, phosphoprotein, nucleoprotein, and a hybrid fusion protein in which the F ectodomain was replaced with the G central region (GCR).
View Article and Find Full Text PDFTetanus is a preventable, yet often fatal, disease affecting many species, including beef cattle. Vaccination for tetanus is recommended for calves at high risk of disease, but typical beef cattle management practices often make adherence to vaccine manufacturers' guidance for a second (booster) dose of vaccine difficult. This study examined the antibody response following a single dose of tetanus toxoid, as well as following booster vaccination at various intervals.
View Article and Find Full Text PDFSARS-CoV-2 patients have been reported to have high rates of secondary infections. is a commensal that is typically found in the respiratory and gastrointestinal tracts. However, it can cause severe disease when a person's immune system is compromised.
View Article and Find Full Text PDFThe human respiratory syncytial virus (RSV) is a major cause of severe respiratory tract disease, and a vaccine is not available. We previously reported a novel live vaccine expressing prefusion-stabilized fusion protein (preF) in place of the native F protein (RSV-preF). As preF is non-functional, RSV-preF was amplified in a production line expressing a functional substitute, and exhibited a single-cycle replication phenotype, which holds several unique potential advantages.
View Article and Find Full Text PDFLive-attenuated Respiratory syncytial virus (RSV) vaccines given intranasally have potential to provide comprehensive protection, including lung-resident immunity. It has however proven challenging to impart both sufficient safety and efficacy in a vaccine. To achieve the latter, we used a trans-complementing approach to generate live single-cycle RSV vaccines expressing the prefusion form (preF) of the viral fusion protein (F), either membrane-anchored or secreted.
View Article and Find Full Text PDFBackground: Respiratory syncytial virus (RSV) is a leading viral respiratory pathogen in infants. The objective of this study was to generate RSV live-attenuated vaccine (LAV) candidates by removing the G-protein mucin domains to attenuate viral replication while retaining immunogenicity through deshielding of surface epitopes.
Methods: Two LAV candidates were generated from recombinant RSV A2-line19F by deletion of the G-protein mucin domains (A2-line19F-G155) or deletion of the G-protein mucin and transmembrane domains (A2-line19F-G155S).
The Oklahoma Shock Nathan Shock Center is designed to deliver unique, innovative services that are not currently available at most institutions. The focus of the Center is on geroscience and the development of careers of young investigators. Pilot grants are provided through the Research Development Core to junior investigators studying aging/geroscience throughout the USA.
View Article and Find Full Text PDFAging is a complex multidimensional process of progressive decline affecting multiple organ systems by a number of processes that are still not well understood. While many studies have focused on the approach of studying aging across multiple organs, assessment of the contribution of individual organs to overall aging processes is under appreciated. The ability to study and compare organs in the context of organismal aging has been documented recently using a geropathology grading platform in laboratory mice.
View Article and Find Full Text PDFAm J Pathol
April 2021
Excessive neutrophil influx, their released neutrophil extracellular traps (NETs), and extracellular histones are associated with disease severity in influenza-infected patients. Neutrophil chemokine receptor CXC chemokine receptor 2 (CXCR2) is a critical target for suppressing neutrophilic inflammation. Herein, temporal dynamics of neutrophil activity and NETosis were investigated to determine the optimal timing of treatment with the CXCR2 antagonist, SCH527123 (2-hydroxy-N,N-dimethyl-3-[2-([(R)-1-(5-methyl-furan-2-yl)-propyl]amino)-3,4-dioxo-cyclobut-1-enylamino]-benzamide), and its efficacy together with antiviral agent, oseltamivir, was tested in murine and piglet influenza-pneumonia models.
View Article and Find Full Text PDF() is a highly virulent, intracellular Gram-negative bacterial pathogen. Acute infection by aerosol route causes pneumonic tularemia, characterized by nodular hemorrhagic lesions, neutrophil-predominant influx, necrotic debris, fibrin deposition, and severe alveolitis. suppresses activity of neutrophils by impairing their respiratory burst and phagocytic activity.
View Article and Find Full Text PDFMannheimia haemolytica colonizes the nasopharynx of cattle and can cause severe fibrinous pleuropneumonia. IgA proteases are metalloendopeptidases released by bacteria that cleave IgA, enhancing colonization of mucosa. The objectives of these studies were to characterize M.
View Article and Find Full Text PDFAn understanding of early-onset mechanisms underlying age-related changes can be obtained by evaluating changes that precede frailty and end of life using histological characterization of age-related lesions. Histopathology-based information as a component of aging studies in mice can complement and add context to molecular, cellular, and physiologic data, but there is a lack of information regarding scoring criteria and lesion grading guidelines. This report describes the validation of a grading system, designated as the geropathology grading platform (GGP), which generated a composite lesion score (CLS) for comparison of histological lesion scores in tissues from aging mice.
View Article and Find Full Text PDFFront Cell Infect Microbiol
December 2019
Exaggerated host innate immune responses have been implicated in severe influenza pneumonia. We have previously demonstrated that excessive neutrophils recruited during influenza infection drive pulmonary pathology through induction of neutrophil extracellular traps (NETs) and release of extracellular histones. Chemokine receptors (CRs) are essential in the recruitment and activation of leukocytes.
View Article and Find Full Text PDFDisruptive innovations in long-range, cost-effective direct template nucleic acid sequencing are transforming clinical and diagnostic medicine. A multidrug resistant strain and a pan-susceptible strain of Mannheimia haemolytica, isolated from pneumonic bovine lung samples, were sequenced at 146× and 111× coverage, respectively with Oxford Nanopore Technologies MinION. De novo assembly produced a complete genome for the non-resistant strain and a nearly complete assembly for the drug resistant strain.
View Article and Find Full Text PDFis an obligate intracellular pathogen with global health and economic impact. Upon infection, resides within a protective niche, the inclusion, wherein it replicates and usurps host cell machinery and resources. The inclusion membrane is the key host-pathogen interface that governs specific protein-protein interactions to manipulate host signaling pathways.
View Article and Find Full Text PDFThe Geropathology Grading Platform (GGP) that is being developed by the Geropathology Research Network provides a grading system that allows investigators to assess biological aging in mice by measuring the pathological status of a wide range of tissues in a standardized scoring system. The GGP is a grading system that generates a numerical score for the total lesions in each tissue, which when averaged over the mice in the cohort provides a composite lesion score (CLS) for each tissue and mouse. In this study, we tested ability of the GGP to predict accelerated aging in mice null for Cu/Zn-superoxide dismutase (Sod1KO mice), which have been shown to have reduced lifespan and healthspan.
View Article and Find Full Text PDFAlthough exaggerated host immune responses have been implicated in influenza-induced lung pathogenesis, the etiologic factors that contribute to these events are not completely understood. We previously demonstrated that neutrophil extracellular traps exacerbate pulmonary injury during influenza pneumonia. Histones are the major protein components of neutrophil extracellular traps and are known to have cytotoxic effects.
View Article and Find Full Text PDFPathobiol Aging Age Relat Dis
April 2017
Pulmonary inflammation and the development of spontaneous lung tumors are important age-related lesions in mice. Therefore, gross and histological examination of the respiratory system is a critical component of geropathology research studies for translating surrogate endpoints to clinical aging studies. Collection, trimming, and processing of lung tissue from aged mice require a high-quality sequential process since aged mice are irreplaceable resource-intensive animal models.
View Article and Find Full Text PDFCalf scours is a primary cause of morbidity and mortality in the dairy industry. Effective treatments are needed to minimize death, maximize welfare, and maintain growth and productivity. The objective of this trial was to compare the efficacy of a commercially available nutritional supplement (Diaque, Boehringer-Ingelheim Vetmedica Inc.
View Article and Find Full Text PDFPhaeohyphomycosis is a rare but emerging disease caused by dematiaceous fungi. Here we describe the case of an immunosuppressed dog with disseminated phaeohyphomycosis secondary to infection. Regionally extensive infiltration of the paw pads, skin, myocardium, liver, renal interstitium and diaphragm was identified on histopathology.
View Article and Find Full Text PDFFront Cell Infect Microbiol
September 2017
is the leading cause of bacterial sexually transmitted infections (STIs) and preventable blindness. Untreated, asymptomatic infection as well as frequent re-infection are common and may drive pelvic inflammatory disease, ectopic pregnancy, and infertility. models of chlamydial infection continue to be instrumental in progress toward a vaccine and further elucidating the pathogenesis of this intracellular bacterium, however significant gaps in our understanding remain.
View Article and Find Full Text PDFCASE DESCRIPTION A 7-year-old castrated male Italian Greyhound (dog 1) and an approximately 1-year-old female Labrador Retriever (dog 2) were evaluated because of respiratory distress 8 and 10 days, respectively, after a tornado. CLINICAL FINDINGS No obvious external injuries were identified auscultation revealed decreased bronchovesicular sounds in the affected hemithorax of both dogs. Clinicopathologic changes were mild, with evidence of inflammation in both dogs.
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