A5036771694- Respiratory viral infections research
- Neonatal Respiratory Health Research
- Congenital Diaphragmatic Hernia Studies
- Pneumonia and Respiratory Infections
- Viral gastroenteritis research and epidemiology
- Influenza Virus Research Studies
- Tracheal and airway disorders
- Parvovirus B19 Infection Studies
- Viral Infections and Vectors
- Orthodontics and Dentofacial Orthopedics
- Viral Infections and Immunology Research
- Cytomegalovirus and herpesvirus research
- Temporomandibular Joint Disorders
- Neonatal and fetal brain pathology
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Transplantation: Methods and Outcomes
- Fetal and Pediatric Neurological Disorders
- Animal Virus Infections Studies
- Domain Adaptation and Few-Shot Learning
- Bacterial Infections and Vaccines
- Dental Implant Techniques and Outcomes
- Herpesvirus Infections and Treatments
- Virology and Viral Diseases
- IL-33, ST2, and ILC Pathways
Enanta Pharmaceuticals (United States)
2022-2025
University of Tennessee Health Science Center
2013-2023
Le Bonheur Children's Hospital
2014-2023
Children’s Foundation
2001-2021
St. Jude Children's Research Hospital
2021
University of Tennessee at Knoxville
2008-2020
Pediatrics and Genetics
2005-2019
Biology of Infection
2018
Engineering Associates (United States)
2018
Pediatric Infectious Diseases Society
2017
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants, and a need exists for prevention RSV healthy infants. Nirsevimab monoclonal antibody with an extended half-life that being developed to protect infants entire season single intramuscular dose.
RNA interference (RNAi) is a natural mechanism regulating protein expression that mediated by small interfering RNAs (siRNA). Harnessing RNAi has potential to treat human disease; however, clinical evidence for the effectiveness of this therapeutic approach lacking. ALN-RSV01 an siRNA directed against mRNA respiratory syncytial virus (RSV) nucleocapsid (N) and substantial antiviral activity in murine model RSV infection. We tested adults experimentally infected with wild-type RSV....
ABSTRACT Secondary bacterial infections often complicate respiratory viral infections, but the mechanisms whereby viruses predispose to disease are not completely understood. We determined effects of infection with syncytial virus (RSV), human parainfluenza 3 (HPIV-3), and influenza on abilities nontypeable Haemophilus influenzae S treptococcus pneumoniae adhere epithelial cells how these alter expression known receptors for bacteria. All enhanced adhesion primary immortalized cell lines....
Rationale: Respiratory syncytial virus (RSV) is the leading cause of childhood lower respiratory infection, yet viable therapies are lacking. Two major challenges have stalled antiviral development: ethical difficulties in performing pediatric proof-of-concept studies and prevailing concept that disease immune-mediated rather than being driven by viral load.Objectives: The development a human experimental wild-type RSV infection model to address these challenges.Methods: Healthy volunteers...
Respiratory syncytial virus (RSV) is a common cause of infant hospitalizations and increasingly recognized as considerable morbidity mortality. No accepted antiviral treatment exists.We conducted double-blind, placebo-controlled study GS-5806, an oral RSV-entry inhibitor, in healthy adults who received clinical challenge strain RSV intranasally. Participants were monitored for 12 days. At the time positive test infection or 5 days after inoculation, whichever occurred first, participants...
Despite relative antigenic stability, respiratory syncytial virus (RSV) reinfects throughout life. After more than 40 years of research, no effective human vaccine exists and correlates protection remain poorly defined. Most current candidates seek to induce high levels RSV-specific serum neutralizing antibodies, which are associated with reduced RSV-related hospitalization rates in observational studies but may not actually prevent infection.
Respiratory syncytial virus (RSV) disease severity was thought to be a result of host immunopathology but alternatively may driven by high-level viral replication. The relationships between RSV load, clearance dynamics, and have not been carefully evaluated.Previously healthy RSV-infected children <2 years old were recruited. load measured in respiratory secretions fresh quantitative culture over 3 hospital days. Measures admission, duration hospitalization, requirement for intensive care,...
BACKGROUND Respiratory syncytial virus (RSV) infection is a cause of substantial morbidity and mortality. There no known effective therapy. METHODS We conducted randomized, double-blind, clinical trial in healthy adults inoculated with RSV. Participants received the oral nucleoside analogue ALS-008176 or placebo 12 hours after confirmation RSV 6 days inoculation. Treatment was administered every for 5 days. Viral load, disease severity, resistance, safety were measured throughout 28-day...
Respiratory syncytial virus (RSV) is the leading, global cause of serious respiratory disease in infants and an important illness older adults. No RSV vaccine currently available. The fusion (F) glycoprotein a key antigen for development, its prefusion conformation target most potent neutralizing antibodies. Here, we describe computational experimental strategy designing immunogens that enhance conformational stability immunogenicity F. We obtained optimized after screening nearly 400...
Thirty-five children <2 years of age mechanically ventilated for respiratory syncytial virus (RSV) infection were randomized to receive an intravenous infusion 15 mg/kg MEDI-493 or placebo. RSV concentration was measured in tracheal secretions by plaque assay before and at 24-h intervals after treatment. The reduction from day 0 1 (-1.7+/-0.28 vs. -0. 6+/-0.21 log10 pfu/mL; P=.004) 2 (-2.5+/-0.26 -1.0+/-0.41 P=.012) significantly greater the group than placebo group. nasal aspirates did not...
Elucidating the relationship between viral load and respiratory syncytial virus (RSV) disease severity is critical to understanding pathogenesis predicting utility of antivirals.Previously healthy, naturally RSV-infected infants <24 months old not treated with ribavirin, passive antibody, or corticosteroids were prospectively studied (n=141). Viral loads measured by fresh quantitative culture from nasal washes collected at a single time point shortly after hospitalization.The subjects' mean...
Lower respiratory tract infections due to syncytial virus (RSV) are associated with development of bronchiolitis obliterans syndrome in lung transplant (LTX) recipients. ALN-RSV01 is a small interfering RNA targeting RSV replication.To determine the safety and explore efficacy infection.We performed randomized, double-blind, placebo-controlled trial LTX recipients infection. Patients were permitted receive standard care for RSV. Aerosolized (0.6 mg/kg) or placebo was administered daily 3...
Children are an at-risk population for developing complications following influenza infection, but immunologic correlates of disease severity not understood. We hypothesized that innate cellular immune responses at the site infection would correlate with outcome.To test basis severe illness during natural virus children and adults infection.An observational cohort study longitudinal sampling peripheral mucosal sites in 84 naturally influenza-infected individuals, including infants. Cellular...
Respiratory syncytial virus (RSV) is the most common cause of infant hospitalizations and severe RSV infections are a significant risk factor for childhood asthma. The pathogenic mechanisms responsible induced immunopathophysiology remain elusive. Using an age-appropriate mouse model RSV, we show that IL-33 plays critical role in immunopathogenesis which associated with higher group 2 innate lymphoid cells (ILC2s) specifically neonates. Infection rapid expression increase ILC2 numbers lungs...
We describe the design and characterization of a potent human respiratory syncytial virus (RSV) nucleocapsid gene-specific small interfering RNA (siRNA), ALN-RSV01. In in vitro RSV plaque assays, ALN-RSV01 showed 50% inhibitory concentration 0.7 nM. Sequence analysis primary isolates that siRNA target site was absolutely conserved 89/95 isolates, demonstrated activity against all including those with single-mismatch mutations. vivo, intranasal dosing BALB/c mouse model resulted antiviral...
Respiratory syncytial virus (RSV) infection is the major cause of bronchiolitis in young children. The factors that contribute to increased propensity RSV-induced distal airway disease compared with other commonly encountered respiratory viruses remain unclear. Here, we identified RSV-encoded nonstructural 2 (NS2) protein as a viral genetic determinant for initiating obstruction. Infection human cartilaginous epithelium (HAE) and hamster model recombinant revealed NS2 promotes shedding...
Two meetings, one sponsored by the Wellcome Trust in 2012 and other Global Virology Foundation 2013, assembled academic, public health pharmaceutical industry experts to assess challenges opportunities for developing antivirals treatment of respiratory syncytial virus (RSV) infections. The practicalities clinical trials establishing reliable outcome measures different target groups were discussed context regulatory pathways that could accelerate translation promising compounds into licensed...
Respiratory syncytial virus (RSV) is a significant cause of severe lower respiratory tract disease in children and older adults, but has no approved vaccine. This study assessed the potential Ad26.RSV.preF to protect against RSV infection an human challenge model.In this double-blind, placebo-controlled study, healthy adults aged 18-50 years were randomized 1:1 receive 1 × 1011 vp or placebo intramuscularly. Twenty-eight days postimmunization, volunteers challenged intranasally with RSV-A...
OBJECTIVE. We sought to determine the epidemiologic features of respiratory syncytial virus infection in immunocompromised pediatric patients and identify risk factors for severe disease. METHODS. designed a retrospective study examining experience with underlying malignancies hematopoietic stem cell transplant recipients seen between 1997 2005. Clinical laboratory data were extracted from patient records, independent predictors disease severity investigated. RESULTS. Fifty-eight met...
ABSTRACT Respiratory syncytial virus (RSV) is the most common cause of lower respiratory infection children. Understanding RSV pathogenesis and evaluating interventions requires quantitative testing. Previous studies have used plaque assay technique. Real-time reverse transcriptase PCR (RTrtPCR) offers possible greater sensitivity, stability after freeze/thaw, cost, thus facilitating multicenter studies. We developed RTrtPCR assays based upon N F genes. The N-gene detected quantity was...