A5103038976- Tuberculosis Research and Epidemiology
- Immune responses and vaccinations
- Mycobacterium research and diagnosis
- Immunodeficiency and Autoimmune Disorders
- bioluminescence and chemiluminescence research
- Diagnosis and treatment of tuberculosis
- Advanced Fluorescence Microscopy Techniques
- vaccines and immunoinformatics approaches
- Photoacoustic and Ultrasonic Imaging
- Cell Image Analysis Techniques
- Low-power high-performance VLSI design
- VLSI and FPGA Design Techniques
- Infant Nutrition and Health
- Optical Imaging and Spectroscopy Techniques
- Immune Response and Inflammation
- Escherichia coli research studies
- Essential Oils and Antimicrobial Activity
- Cancer Research and Treatments
- Biosensors and Analytical Detection
- Advanced Optical Network Technologies
- Pneumonia and Respiratory Infections
- Listeria monocytogenes in Food Safety
- Salmonella and Campylobacter epidemiology
London School of Hygiene & Tropical Medicine
2012-2024
University of London
2012-2024
Medway School of Pharmacy
2010
German Center for Infection Research
2005
Background Mycobacterium tuberculosis, the causative agent of still represents a major public health threat in many countries. Bioluminescence, production light by luciferase-catalyzed reactions, is versatile reporter technology with multiple applications both vitro and vivo. In vivo bioluminescence imaging (BLI) one its most outstanding uses allowing non-invasive localization luciferase-expressing cells within live animal. Despite extensive use luminescent reporters mycobacteria, resultant...
The current method for testing new drugs against tuberculosis in vivo is the enumeration of bacteria organs by cfu assay. Owing to slow growth rate Mycobacterium (Mtb), these assays can take months complete. Our aim was develop a more efficient, fluorescence-based imaging assay test antibiotics mouse model using Mtb reporter strains. A commercial IVIS Kinetic® system and custom-built laser scanning with fluorescence molecular tomography (FMT) capability were used detect fluorescent living...
ObjectivesIn vivo experimentation is costly and time-consuming, presents a major bottleneck in anti-tuberculosis drug development. Conventional methods rely on the enumeration of bacterial colonies, it can take up to 4 weeks for Mycobacterium tuberculosis grow agar plates. Light produced by recombinant bacteria expressing luciferase enzymes be used as marker load, disease progression easily followed non-invasively live animals using appropriate imaging equipment. The objective this work was...
Vaccination with Bacillus Calmette Guerin (BCG) protects infants against childhood tuberculosis however the immune mechanisms involved are not well understood. Further elucidation of infant response to BCG will aid identification correlates protection and design new improved vaccines. The purpose this study was investigate BCG-induced CD4+ T-cell responses in blood samples from for cytokine secretion profiles thought be important compare these PBMC-mediated vitro mycobacterial growth...
Human tuberculosis (TB) is caused by various members of the Mycobacterium (Mtb) complex. Differences in host response to infection have been reported, illustrative a need evaluate efficacy novel vaccine candidates against multiple strains preclinical studies. We previously showed that murine lung and spleen direct mycobacterial growth inhibition assay (MGIA) can be used assess control ex vivo cells. The number mice required for significantly lower than studies, facilitating testing and/or...
In the absence of a validated animal model and/or an immune correlate which predict vaccine-mediated protection, large-scale clinical trials are currently only option to prove efficacy new tuberculosis candidate vaccines. Tools facilitate testing (TB) vaccines therefore urgently needed.We present here optimized ex vivo mycobacterial growth inhibition assay (MGIA) using murine Mycobacterium infection model. This assesses combined ability host cells inhibit in response vaccination. C57BL/6...
Tuberculosis (TB) is a major global health problem and there dire need for an improved treatment. A strategy to combine vaccination with drug treatment, termed therapeutic vaccination, expected provide benefit in shortening treatment duration augmenting success rate. RUTI candidate vaccine has been specifically developed as TB. The shown reduce bacillary load when administered after chemotherapy murine guinea pig models, also immunogenic given healthy adults individuals latent In the absence...
Many neurotropic strains of Escherichia coli cause potentially lethal bacteraemia and meningitis in newborn infants by virtue their capacity to elaborate the protective polysialic acid (polySia) K1 capsule. Recombinant capsule depolymerase, endosialidase E (endoE), selectively removes polySia from bacterial surface; when administered intraperitoneally infected neonatal rats, enzyme interrupts transit E. gut brain via blood circulation prevents death systemic infection. We now show that...
In vaccine development, dose-response curves are commonly assumed to be saturating. Evidence from tuberculosis (TB) vaccine, H56 + IC31 shows this may incorrect. Mathematical modelling techniques useful in efficiently identifying the most immunogenic dose, but model calibration requires longitudinal data across multiple doses and time points. We aimed (i) generate response mice for a wide range of use future mathematical (ii) test whether 'saturating' or 'peaked' curve, better fit empirical...
In the absence of a correlate(s) protection against human tuberculosis and validated animal model disease, tools to facilitate vaccine development must be identified. We present an optimised ex vivo mycobacterial growth inhibition assay (MGIA) assess ability host cells within lung inhibit growth, including Bacille Calmette-Guérin (BCG) Mycobacterium (MTB) Erdman. Growth BCG was reduced by 0.39, 0.96 0.73 log10 CFU following subcutaneous (s.c.) BCG, intranasal (i.n.) or s.c. + mucosal boost,...
Abstract Tuberculosis (TB) is a leading infectious cause of death globally. Drug treatment and vaccination, in particular with Bacillus Calmette-Guérin (BCG), remain the main strategies to control TB. With emergence drug resistance, it has been proposed that combination TB vaccination pharmacological may provide greater therapeutic value. We implemented an ex vivo mycobacterial growth inhibition assay (MGIA) discriminate vaccine responses historically BCG-vaccinated human volunteers assess...
Background: It is important to understand the ability inhibit mycobacterial growth in healthy adults who would have been Bacillus Calmette-Guérin (BCG) vaccinated childhood as this group will be potential target population for novel booster TB vaccine trials. In study we investigated not only long-term immunity induced by BCG vaccination but also protective terms of those were childhood, with evidence recent or remote infection. Methods: We measured baseline immune response using a...
The testing of vaccines for tuberculosis is costly and time-consuming, dependent on preclinical animal challenge models clinical trials. We have recently developed a mycobacterial growth inhibition assay (MGIA) to test vaccine efficacy ex vivo. This measures the summative effect host immune response may serve as novel tool facilitate testing. It has generated much interest recently, technology transfer reproducibility between laboratories, we here describe detailed protocol an vivo MGIA in...
<ns4:p><ns4:bold>Background:</ns4:bold>The only available tuberculosis (TB) vaccine, Bacillus Calmette-Guérin (BCG), has variable efficacy. New vaccines are therefore urgently needed. Why BCG fails is incompletely understood, and the tools used for early assessment of new vaccine candidates do not account variability. Taking correlates risk TB disease observed in human studies back-translating them into mice to create models variability should allow novel be tested animal that more...
<ns4:p><ns4:bold>Background: </ns4:bold>The only available tuberculosis (TB) vaccine, Bacillus Calmette-Guérin (BCG), has variable efficacy. New vaccines are therefore urgently needed. Why BCG fails is incompletely understood, and the tools used for early assessment of new vaccine candidates do not account variability. Taking correlates risk TB disease observed in human studies back-translating them into mice to create models variability should allow novel be tested animal that more...
Abstract Tuberculosis (TB) vaccine candidates must be tested for safety and efficacy using preclinical challenge models prior to advancement human trials, because of the lack a validated immune correlate or biomarker protection. New, unbiased tools are urgently needed expedite selection at an early stage development reduce number animals experimentally infected with virulent Mycobacterium tuberculosis ( M . tb ). In recent years, there has been concerted effort develop standardised...