A5013597261- Escherichia coli research studies
- Viral gastroenteritis research and epidemiology
- Clostridium difficile and Clostridium perfringens research
- Immunotherapy and Immune Responses
- Anesthesia and Pain Management
- Systemic Sclerosis and Related Diseases
- Muscle metabolism and nutrition
- Salmonella and Campylobacter epidemiology
- Enzyme Production and Characterization
- Medical and Biological Ozone Research
- Retinal Diseases and Treatments
- Corneal surgery and disorders
- Glaucoma and retinal disorders
- Autoimmune and Inflammatory Disorders Research
- Nutrition, Genetics, and Disease
- T-cell and B-cell Immunology
- Multiple Sclerosis Research Studies
- Urticaria and Related Conditions
- Anesthesia and Sedative Agents
- Bacterial Infections and Vaccines
- Enzyme Catalysis and Immobilization
- Biofuel production and bioconversion
- Health, psychology, and well-being
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Electrolyte and hormonal disorders
Walter Reed Army Institute of Research
2015-2024
Amgen (United States)
2024
Horizon Therapeutics (United States)
2023
Northwestern University
1996
St. James's Hospital
1995
St. Vincent's Birmingham
1990
ABSTRACT Several candidate vaccines against Shigella spp. are in development, but the lack of a clear correlate protection from challenge with induction adequate immune responses among youngest age groups developing world has hampered vaccine development over past several decades. Bioconjugation technology, exploited here for an flexneri 2a vaccine, offers novel and potentially cost-effective way to develop produce major pathogen global health importance. Flexyn2a, S. bioconjugate made...
BackgroundShigellosis is a major cause of moderate to severe diarrhoea and dysentery in children under 5 years age low middle-income countries. The Flexyn2a vaccine conjugates the O-polysaccharide Shigella flexneri 2a Pseudomonas aeruginosa exotoxin A. We describe Phase 2b proof-of-concept challenge study that evaluated safety, immunogenicity, efficacy protect against shigellosis.MethodsIn this randomized, double blind, placebo-controlled trial, healthy adults were randomized 1:1 receive (10...
Shigellosis accounts for substantial morbidity and mortality worldwide is the second most common cause of moderate severe diarrhoea in children.This phase 2b study (NCT03527173), conducted between August 2018 November 2019, evaluated vaccine efficacy (VE), safety, immunogenicity a Shigella sonnei GMMA candidate (1790GAHB) adults, using S. 53 G controlled human infection model. Participants (randomized 1:1) received two doses 1790GAHB or placebo (GAHB-Placebo), at day (D) 1 D29, an oral...
BackgroundDiarrheal diseases are a leading cause of global morbidity and mortality affecting all ages, but especially children under the age five in resource-limited settings. Shigella is contributor to diarrheal caused by bacterial pathogens considered significant antimicrobial resistance threat. While improvements hygiene, access clean water help as control measures, vaccination remains one most viable options for significantly reducing mortality.MethodsFlexyn2a bioconjugate vaccine...
ABSTRACT Studies were undertaken to manufacture a multivalent Shigella inactivated whole-cell vaccine that is safe, effective, and inexpensive. By using several formalin concentrations, temperatures, incubation periods, an optimized set of inactivation conditions was established for flexneri 2a, S. sonnei , 3a produce whole cells expressing full repertoire Ipa proteins lipopolysaccharide (LPS). The selected treatment with 0.2% ( 2a 3a) or 0.6% ) 48 h at 25°C. Vaccine formulations prepared...
The native Invaplex (InvaplexNAT) vaccine and adjuvant is an ion exchange-purified product derived from the water extract of virulent Shigella species. key component InvaplexNAT a high-molecular-mass complex (HMMC) consisting lipopolysaccharide (LPS) invasin proteins IpaB IpaC. To improve purity immunogenicity, artificial (InvaplexAR) was developed using recombinant IpaC purified LPS to assemble HMMC all three components. Characterization InvaplexAR by various methods demonstrated similar...
Shigella is a major cause of moderate to severe diarrhea largely affecting children (<5 years old) living in low- and middle-income countries. Several vaccine candidates are development, controlled human infection models (CHIMs) can be useful tools provide an early assessment efficacy potentially support licensure. A lyophilized strain S. sonnei 53G was manufactured evaluated establish dose that safely reproducibly induced ≥60% attack rate. Samples were collected pre- postchallenge assess...
BackgroundShigella is the third leading global cause of moderate or severe diarrhoea among children younger than 5 years globally, and in aged 24–59 months. The mechanism protection against Shigella infection disease endemic areas uncertain. We aimed to compare Shigella-specific antibody responses individuals living Shigella-endemic non-endemic areas, identify correlates a location.MethodsWe applied systems approach retrospectively analyse serological across populations. profiled serum...
Abstract Moderate to severe diarrhea caused by Shigella is a global health concern due its substantial contribution morbidity and mortality in children aged &lt;5 years low- middle-income countries. Although antibiotic treatment can be effective, emerging antimicrobial resistance, limited access, cost affirm the role of vaccines as most attractive countermeasure. Controlled human infection models (CHIMs) represent valuable tool for assessing vaccine efficacy potentially accelerating...
Abstract Shigella spp. are a leading bacterial cause of diarrhea. No widely licensed vaccines available and there is no generally accepted correlate protection. We tested S. sonnei Generalized Modules for Membrane Antigen (GMMA)-based vaccine (1790GAHB) in phase 2b, placebo-controlled, randomized, controlled human infection model study (NCT03527173) enrolling healthy United States adults aged 18–50 years. report analyses evaluating immune responses to vaccination, with the aim identify...
Controlled human infection models (CHIMs) are useful for vaccine development. To improve on existing models, we developed a CHIM using lyophilized preparation of Shigella sonnei strain 53G produced current good manufacturing practice (cGMP). Healthy adults were enrolled in an open-label dose-ranging study. Following administration dose rehydrated S. 53G, subjects monitored development disease. The first cohort received 500 CFU and dosing subsequent cohorts was based results from the previous...
Shigella spp. are a leading cause of diarrhea-associated global morbidity and mortality. Development widespread implementation an efficacious vaccine remain the best option to reduce Shigella-specific morbidity. Unfortunately, lack well-defined correlate protection for shigellosis continues hinder development efforts. controlled human infection models (CHIM) often used in early stages provide preliminary estimates efficacy; however, CHIMs also opportunity conduct in-depth immune response...
The Shigella artificial invasin complex (InvaplexAR) vaccine is a subunit approach that effectively induces robust immunogenicity directed to serotype-specific lipopolysaccharide and the broadly conserved IpaB IpaC proteins. One advantage of ability adjust constituents address suboptimal change serotype targeted by vaccine. As moves through product development pipeline, substantial modifications have been made manufacturing feasibility, acceptability regulatory authorities, developing...
Shigella species cause severe disease among travelers to, and children living in, endemic countries. Although significant efforts have been made to improve sanitation, increased antibiotic resistance other factors suggest an effective vaccine is a critical need. Artificial Invaplex (InvaplexAR) subunit approach complexing LPS with invasion plasmid antigens. In pre-clinical studies, the InvaplexAR demonstrated immunogenicity as compared first generation product was subsequently manufactured...
In order to avoid expensive clinical failures, better and more predictive animal models of vaccine efficacy are needed screen Shigella ETEC candidates for protective efficacy. The 2016 Vaccines Against (VASE) Conference included a workshop focused on the strengths weaknesses current models, particularly in terms correlation human trials. Workshop presenters shared information existing preclinical assessing immunogenicity vaccines. presentations were followed by discussion about how best...
To evaluate the relationship between cytokine levels and disease activity in Neuromyelitis Optica Spectrum Disorder (NMOSD) participants from N-MOmentum (NCT02200770).
Abstract Background Previous studies have shown an association between post-traumatic stress disorder (PTSD) and the development of irritable bowel syndrome (IBS) in deployed service members. Deployment places soldiers at risk for chemical, physical, psychological, infectious stressors. Acute can alter gastrointestinal barrier leading to gut dysfunction, which is independent factor gastroenteritis (IGE). We sought assess if there was IBS PTSD military support recent ongoing operations....