A5043448395- Immune Cell Function and Interaction
- Immune responses and vaccinations
- Cancer Research and Treatments
- Protein Structure and Dynamics
- Immunotherapy and Immune Responses
- Tuberculosis Research and Epidemiology
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Diabetes and associated disorders
- Escherichia coli research studies
- Nanoplatforms for cancer theranostics
- Transgenic Plants and Applications
- Immune Response and Inflammation
- Viral gastroenteritis research and epidemiology
- Alzheimer's disease research and treatments
- Phagocytosis and Immune Regulation
- Xenotransplantation and immune response
- Monoclonal and Polyclonal Antibodies Research
- Computational Drug Discovery Methods
- Bacterial Infections and Vaccines
- Bacteriophages and microbial interactions
- Plant Virus Research Studies
- Machine Learning in Bioinformatics
University of Birmingham
2018-2025
St George's, University of London
2017-2023
University College London
2013-2014
University of Sussex
2009-2010
University of Liverpool
2009
Introduction. Campylobacter jejuni is a leading cause of bacterial gastroenteritis worldwide. At present the identity host-pathogen interactions that promote successful colonisation remain ill defined. Herein, we aimed to investigate C. jejuni-mediated effects on dendritic cell (DC) immunity. Results. We found be potent inducer human and murine DC interleukin 10 (IL-10) in vitro, cellular event was MyD88- p38 MAPK-signalling dependent. Utilizing series isogenic mutants major flagellin...
How T cell receptor (TCR) signal strength modulates function and to what extent this is modified by immune checkpoint blockade (ICB) are key questions in immunology. Using Nr4a3-Tocky mice, we characterized early quantitative qualitative changes that occur CD4+ cells relation TCR signaling strength. We captured how dose- time-dependent programming of distinct co-inhibitory receptors rapidly recalibrates activation thresholds visualized the immediate effects ICB on re-activation. Our findings...
Tuberculosis (TB) is the most deadly infectious disease in existence, and only available vaccine, Bacillus Calmette-Guérin (BCG), almost a century old poorly protective. The immunological complexity of TB, coupled with rising resistance to antimicrobial therapies, necessitates pipeline diverse novel vaccines. Here, we show that B. subtilis spores can be coated fusion protein ('FP1') consisting M. tuberculosis (Mtb) antigens Ag85B, ACR HBHA. resultant Spore-FP1, was tested murine low-dose Mtb...
Tuberculosis (TB) is the leading cause of death from infectious disease, and current vaccine, Bacillus Calmette-Guerin (BCG), inadequate. Nanoparticles (NPs) are an emerging vaccine technology, with recent successes in oncology diseases. NPs have been exploited as antigen delivery systems also for their adjuvantic properties. However, mechanisms underlying immunological activity remain obscure. Here, we developed a novel mucosal TB (Nano-FP1) based upon yellow carnauba wax (YC-NPs), coated...
In order to enhance vaccine uptake by the immune cells in vivo, molecular engineering approach was employed construct a polymeric immunoglobulin G scaffold (PIGS) that incorporates multiple copies of an antigen and targets Fc gamma receptors on antigen-presenting cells. These self-adjuvanting immunogens were tested context dengue infection, for which there is currently no globally licensed yet. Thus, consensus domain III sequence (cEDIII) glycoprotein E incorporated into PIGS expressed both...
Dengue is a major global disease requiring improved treatment and prevention strategies. The recently licensed Sanofi Pasteur Dengvaxia vaccine does not protect children under the age of nine, additional strategies are thus needed to halt this expanding epidemic. Here, we employed molecular engineering approach plant expression produce humanized highly immunogenic poly-immunoglobulin G scaffold (PIGS) fused consensus dengue envelope protein III domain (cEDIII). immunogenicity IgG Fc...
Abstract Bacillus Calmette-Guérin (BCG) is the only licensed vaccine for tuberculosis (TB), and also used as an immunotherapy bladder cancer other malignancies due to its immunostimulatory properties. Mycobacteria spp., however, are well known their numerous immune evasion mechanisms that limit true potential of therapeutic use. One such major mechanism induction programmed death ligand-1 (PD-L1), which mitigates adaptive responses. Here, we sought unravel molecular pathways behind PD-L1...
Strong T cell receptor (TCR) and interleukin (IL)-27 signaling influence type 1 regulatory (Tr1) development, but whether other signals determine their differentiation is unclear. Utilizing Tg4 TCR transgenic mice, we established a model for rapid Tr1 induction. A single high dose of [4Y]-MBP peptide drove the Il10 + cells with mRNA protein signatures. Kinetic transcriptional phenotypic analyses revealed that module was transient preceded by Ifng transcription in CD4+ cells. Changes...
Lag3 and PD-1 are immune checkpoints that regulate T cell responses current immunotherapy targets. Yet how they function to control early stages of CD4+ activation remains unclear. Here, we show the pathways exhibit layered process, with effects more pronounced in presence pathway co-blockade (CB). RNA sequencing revealed CB drove an NFAT-dependent transcriptional profile, including promotion ICOShi follicular helper differentiation. NFAT inhibition abolished CB-induced upregulation...
Liposomes have been long considered as a vaccine delivery system but this technology remains to be fully utilised. Here, we describe novel liposome-based subunit formulation for tuberculosis (TB) based on phosphatidylserine encapsulating two prominent TB antigens, Ag85B and ESAT-6. We show that the resulting liposomes (Lipo-AE) are stable upon storage can readily taken up by both mouse human antigen presenting cells their antigenic cargo is delivered processed within endosomal cell...
New evidence has been emerging that antibodies can be protective in various experimental models of tuberculosis. Here, we report on protection against multidrug-resistant Mycobacterium tuberculosis (MDR-TB) infection using a combination the human monoclonal IgA 2E9 antibody alpha-crystallin (Acr, HspX) antigen and mouse interferon-gamma mice transgenic for receptor, CD89. The effect combined mucosal IFN-γ; treatment was strongest (50-fold reduction) when therapy applied at time infection,...
Vaccination is considered the most effective strategy for controlling tuberculosis (TB). The existing vaccine, Bacille Calmette-Guérin (BCG), although partially protective, has a number of limitations. Therefore, there need developing new TB vaccines and several strategies are currently exploited including use viral bacterial delivery vectors. We have previously shown that Lactobacillus plantarum (Lp) producing Ag85B ESAT-6 antigens fused to dendritic cell-targeting peptide (referred as...
Over 30 polypeptides are known to assemble into highly ordered fibrils associated with pathological disorders collectively as amyloidoses. Structural studies of short model peptides beginning reveal trends in the types molecular interactions that drive aggregation and stabilize packing beta-sheet layers within fibrillar assemblies. This work investigates architecture formed by peptide AMed42-49 representing residues 42-49 50 amino acid polypeptide medin aortic medial amyloid, most common...
Summary In this study, a strategy based on polymeric immunoglobulin G scaffolds ( PIGS ) was used to produce vaccine candidate for Mycobacterium tuberculosis . A genetic fusion construct comprising genes encoding the mycobacterial Ag85B antigen, an γ‐chain fragment and tailpiece from μ chain engineered. Expression attempted in Chinese Hamster Ovary CHO cells Nicotiana benthamiana The recombinant protein assembled into structures TB ‐ N. , similar size IgM. These complexes were subsequently...
Tuberculosis remains a major health threat globally and more effective vaccine than the current Bacillus Calmette Guerin (BCG) is required, either to replace or boost it. The Spore-FP1 mucosal candidate based on fusion protein of Ag85B-Acr-HBHA/heparin-binding domain, adsorbed surface inactivated subtilis spores. conferred significant protection against Mycobacterium. tuberculosis challenge in naïve guinea pigs markedly improved lungs spleens animals primed with BCG. We then immunized rhesus...
Outer membrane vesicles (OMV) are released by many bacteria, and contain immunogenic antigens in addition to harmful inflammatory factors, like lipopolysaccharides. Chemically detoxified OMV have been used vaccines against Neisseria meningitidis (Nm); however, little is known about their interaction with antigen presenting cells. In this study, we investigated the of Nm human dendritic cells (DC) gain further understanding biological activity. We engineered a novel serogroup B that...
Bacterial cancer therapy (BCT) shows great promise for treatment of solid tumors, yet basic mechanisms bacterial-induced tumor suppression remain undefined. Attenuated strains Salmonella enterica serovar Typhimurium (STm) have commonly been used in mouse models BCT xenograft and orthotopic transplant models. We aimed to better understand the epithelium–targeted by using autochthonous intestinal organoid cultures assess effectiveness consequences oral with aromatase A–deficient STm...
Abstract Bacterial cancer therapy (BCT) shows great promise for treatment of solid tumors, yet basic mechanisms bacterial-induced tumor suppression remain undefined. The intestinal epithelium is the natural route infection Salmonella and thus harbors innate immune defenses which protect against infection. Attenuated strains enterica serovar Typhimurium ( S Tm) have commonly been used in mouse models BCT, largely with use xenograft orthotopic transplant models. We aimed to better understand...
A comprehensive study by van der Sluis et al.1van T.C. Beyrend G. Gracht E.T. Abdelaal T. Jochems S.P. Belderbos R.A. Wesselink T.H. Duikeren S. Haften F.J. Redeker A. al.OX40 agonism enhances PD-L1 checkpoint blockade shifting the cytotoxic T cell differentiation spectrum.Cell Reports Medicine. 2023; (100939): 100939https://doi.org/10.1016/j.xcrm.2023.100939Abstract Full Text PDF PubMed Scopus (2) Google Scholar demonstrates immunotherapeutic targeting of OX40 and results in enhanced tumor...
Abstract Anti-Lag3 and anti-PD-1 combination immunotherapy for melanoma has received recent regulatory approval, yet its mechanism of action is unclear, particularly CD4 + T cells. Here, we determined the roles Lag3 PD-1/PD-L1 pathways during cell activation in vivo . During primary immune responses, played a redundant role with PD1/PD-L1 axis dominant regulating early activation. By exploiting an adaptive tolerance model, reveal that PD-L1 co-blockade (CB) drove major changes cells,...