A5077287298- Viral gastroenteritis research and epidemiology
- Viral Infections and Immunology Research
- Asthma and respiratory diseases
- Allergic Rhinitis and Sensitization
- Inflammatory Bowel Disease
- Respiratory and Cough-Related Research
- Viral Infectious Diseases and Gene Expression in Insects
- Helicobacter pylori-related gastroenterology studies
- Animal Virus Infections Studies
- Virus-based gene therapy research
- Polyomavirus and related diseases
- Urticaria and Related Conditions
- Pharmaceutical studies and practices
- Plant Virus Research Studies
- Animal Disease Management and Epidemiology
- Microscopic Colitis
- Adrenal and Paraganglionic Tumors
- Biliary and Gastrointestinal Fistulas
- Vagus Nerve Stimulation Research
- Eosinophilic Esophagitis
- High Altitude and Hypoxia
- Mast cells and histamine
- SARS-CoV-2 and COVID-19 Research
- Cardiac tumors and thrombi
- Diverticular Disease and Complications
National Institute for Biological Standards and Control
2015-2023
Heart and Diabetes Center North Rhine-Westphalia
2017-2019
Potters Bar Community Hospital
2019
Novartis (United Kingdom)
2004-2006
Novartis (Switzerland)
2004
Salford Royal Hospital
1975-1976
University of Manchester
1975-1976
Manchester Royal Infirmary
1975-1976
Summary Background Patients with severe asthma are often inadequately controlled on existing anti‐asthma therapy, constituting an unmet clinical need. Objective This randomized, double‐blind, placebo‐controlled trial evaluated the ability of omalizumab, a humanized monoclonal anti‐IgE antibody, to improve disease control sufficiently enable inhaled corticosteroid reduction in patients allergic asthma. Methods After run‐in period when optimized fluticasone dose (1000 μg/day) was received for...
Background: Anti‐IgE therapy could be particularly beneficial for patients with concomitant disease as it targets a common factor in both diseases. The aim of this study was to evaluate the efficacy and safety omalizumab moderate‐to‐severe asthma persistent allergic rhinitis. Methods: This multicentre, randomized, double‐blind, parallel‐group, placebo‐controlled trial evaluated omalizumab. A total 405 (12–74 years) stable treatment (≥ 400 μ g budesonide Turbuhaler ® ) ≥ 2 unscheduled medical...
Background: Patients with poorly controlled asthma have greater morbidity and mortality. This study evaluated the efficacy tolerability of omalizumab in patients controlled, moderate‐to‐severe allergic asthma. Methods: was a randomized, open‐label, multicentre, parallel‐group study. A total 312 (12–73 years) receiving ≥400 μ g/day (adolescent) or ≥800 (adult) inhaled beclomethasone dipropionate, equivalent were included. received best standard care (BSC) without [at least 0.016 mg/kg/IgE...
Poliovirus (PV) is the causative agent of poliomyelitis, a crippling human disease known since antiquity. PV occurs in two distinct antigenic forms, D and C, which only form elicits robust neutralizing response. Developing synthetically produced stabilized virus-like particle (sVLP)-based vaccine with antigenicity, without drawbacks current vaccines, will be major step towards final eradication poliovirus. Such sVLP would retain native conformation repetitive structure original virus...
The numbers of mast cells and IgE-containing immunocytes in the bowel wall patients suffering from Crohn's disease ulcerative colitis have been estimated results compared with those found normal control specimens. In there is a slight rise number it appears that these participate inflammatory process non-specific manner; not significantly altered. an almost total absence stainable affected areas bowel, together marked decrease immunocytes. It suggested findings are due to degranulation...
While wild type polio has been nearly eradicated there will be a need to continue immunisation programmes for some time because of the possibility re-emergence and existence long term excreters poliovirus. All vaccines in current use depend on growth virus most non-replicating (inactivated) involve viruses known cause poliomyelitis. The attenuated vaccine strains involved eradication programme have used develop new inactivated as production is thought safer. However it that Sabin are...
Abstract Global vaccination programs using live-attenuated oral and inactivated polio vaccine (OPV IPV) have almost eradicated poliovirus (PV) but these vaccines or their production pose significant risk in a polio-free world. Recombinant PV virus-like particles (VLPs), lacking the viral genome, represent safe next-generation vaccines, however requires optimisation. Here we present an efficient mammalian expression strategy producing good yields of wild-type VLPs for all three serotypes...
Abstract Polioviruses have caused crippling disease in humans for centuries, prior to the successful development of vaccines mid-1900’s, which dramatically reduced prevalence. Continued use these vaccines, however, threatens ultimate eradication and achievement a polio-free world. Virus-like particles (VLPs) that lack viral genome represent safer potential vaccine, although they require particle stabilization. Using our previously established genetic techniques stabilize structural capsid...
Abstract The success of the poliovirus (PV) vaccines has enabled near-eradication wild PV, however, their continued use post-eradication poses concerns, due to potential for virus escape during vaccine manufacture. Recombinant virus-like particles (VLPs) that lack viral genome remove this risk. Here, we demonstrate production PV VLPs all three serotypes by controlled fermentation using Pichia pastoris . We determined cryo-EM structure a new PV2 mutant, termed SC5a, in comparison PV2-SC6b...
Enterovirus A71 (EVA71) causes widespread disease in young children with occasional fatal consequences. In common other picornaviruses, both empty capsids (ECs) and infectious virions are produced during the viral lifecycle. While initially antigenically indistinguishable from virions, ECs readily convert to an expanded conformation at moderate temperatures. closely related poliovirus, these conformational changes result loss of antigenic sites required elicit protective immune responses....
Poliomyelitis has nearly been eradicated through the efforts of World Health Organization's Global Eradication Initiative raising questions on containment virus after it eliminated in wild. Most manufacture inactivated polio vaccines currently requires growth large amounts highly virulent poliovirus, and release from a production facility eradication could be disastrous; WHO have therefore recommended use attenuated Sabin strains for as safer option although is recognised that they can...
Abstract Strategies to prevent the recurrence of poliovirus (PV) after eradication may utilise non-infectious, recombinant virus-like particle (VLP) vaccines. Despite clear advantages over inactivated or attenuated virus vaccines, instability VLPs can compromise their immunogenicity. Glutathione (GSH), an important cellular reducing agent, is a crucial co-factor for morphogenesis enteroviruses, including PV. We report cryo-EM structures GSH bound PV serotype 3 showing that it enhance...
Abstract Polioviruses have caused crippling disease in humans for centuries, prior to the successful development of vaccines mid-1900’s, which dramatically reduced prevalence. Continued use these vaccines, however, threatens ultimate eradication and achievement a polio-free world. Virus-like particles (VLPs) that lack viral genome represent safer potential vaccine, although they require particle stabilization. Using our previously established genetic techniques stabilize structural capsid...
Genetic recombination in RNA viruses is an important evolutionary mechanism. It contributes to population diversity, host/tissue adaptation, and compromises vaccine efficacy. Both the molecular mechanism initial products of are relatively poorly understood. We used established poliovirus-based vitro assay investigate roles sequence identity structure, implicated or inferred from analysis circulating recombinant viruses, process. In addition, we next-generation sequencing early after cellular...
Enterovirus A71 (EVA71) is a medically important virus that commonly associated with hand, foot, and mouth disease (HFMD). It responsible for periodic outbreaks, resulting in significant economic impact loss of life. Vaccination offers the potential to control future vaccine development has been increasingly focus global research efforts. However, antigenic characterization candidates challenging because there are few tools characterize different forms virus. As other picornaviruses, EVA71...
Enterovirus A71 (EVA71) infection can result in paralysis and may be fatal. In common with other picornaviruses, empty capsids are produced alongside infectious virions during the viral lifecycle. These antigenically indistinguishable from virus, but at moderate temperatures they converted to an expanded conformation. closely related poliovirus, native antigenic forms of particle have different long-term protective efficacies when used as vaccines. The form provides long-lived immunity,...
Abstract Genetic recombination in RNA viruses is an important evolutionary mechanism. It contributes to population diversity, host/tissue adaptation and compromises vaccine efficacy. Both the molecular mechanism initial products of are relatively poorly understood. We used established poliovirus-based vitro assay investigate roles sequence identity structure, both implicated or inferred from analysis circulating recombinant viruses, process. In addition, we next generation sequencing early...
BACKGROUND Wild‐type poliovirus may be eradicated soon and under WHO GAPIII guidance, laboratory use will discontinued or subject to strict containment. Per US Code of Federal Regulations, however, immunoglobulin lot release testing still require replicating poliovirus. The suitability S19 hyper‐attenuated apathogenic strains as alternatives the currently used wild‐type virus in such a assay was investigated. STUDY DESIGN AND METHODS were propagated commercial setting using good virological...
Abstract Strategies to prevent the recurrence of poliovirus (PV) after eradication may utilise non-infectious, recombinant virus-like particle (VLP) vaccines. Despite clear advantages over inactivated or attenuated virus vaccines, instability VLPs can compromise their immunogenicity. Glutathione (GSH), an important cellular reducing agent, is a crucial co-factor for morphogenesis enteroviruses, including PV. We report cryo-EM structures GSH bound PV serotype 3 showing that it enhance...
Abstract The success of the poliovirus (PV) vaccines has enabled near-eradication wild PV, however, their continued use post-eradication poses a significant threat to maintaining polio-free world. Recombinant virus-like particles (VLPs) that lack viral genome remove this risk. Here, we demonstrate production PV VLPs for all three serotypes by controlled fermentation using Pichia pastoris . We determined cryo-EM structure new PV-2 mutant, termed SC5a, in comparison SC6b described previously...
Enterovirus A71 (EVA71) causes widespread disease in young children with occasional fatal consequences. In common other picornaviruses, both empty capsids (ECs) and infectious virions are produced during the viral lifecycle. While initially antigenically indistinguishable from virions, ECs readily convert to an expanded conformation at moderate temperatures. closely related poliovirus, these conformational changes result loss of antigenic sites required elicit protective immune responses....