A5064510316- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Transgenic Plants and Applications
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Immunodeficiency and Autoimmune Disorders
- Immune Response and Inflammation
- CRISPR and Genetic Engineering
- Immune responses and vaccinations
- T-cell and B-cell Immunology
- Plant Virus Research Studies
- Glycosylation and Glycoproteins Research
- Pneumocystis jirovecii pneumonia detection and treatment
- Viral gastroenteritis research and epidemiology
- Mosquito-borne diseases and control
- Plant tissue culture and regeneration
- Toxin Mechanisms and Immunotoxins
- Escherichia coli research studies
- Bacteriophages and microbial interactions
- Infectious Diseases and Mycology
- Galectins and Cancer Biology
- Cytokine Signaling Pathways and Interactions
- Immune cells in cancer
St George's, University of London
2016-2025
City St George's, University of London
2025
St. George's University
2024
Institute of Infection and Immunity
2014
St. George's School
2014
Universidad de Londres
2014
St George's Hospital
2014
St George's Hospital
2006-2011
King's College London
1997-2007
University of London
2006-2007
Lymphocytes usually differentiate into effector cells within days after antigen exposure, except in germinal centers where terminal differentiation is delayed while somatic hypermutation creates high-affinity antibody mutants. Here we investigate whether arrest of can be mediated by BCL-6, a transcriptional repressor that expressed center B and required for this phase cell development. We find BCL-6 suppresses the transformed primary to plasma inhibiting signal transducer activator...
Abstract Abs have been shown to be protective in passive immunotherapy of tuberculous infection using mouse experimental models. In this study, we report on the properties a novel human IgA1, constructed single-chain variable fragment clone (2E9), selected from an Ab phage library. The purified monomer revealed high binding affinities for mycobacterial α-crystallin Ag and FcαRI (CD89) IgA receptor. Intranasal inoculations with 2E9IgA1 recombinant IFN-γ significantly inhibited pulmonary H37Rv...
Summary We report on a new approach toward protection against tuberculosis, based passive inoculation with immunoglobulin A (IgA) antibodies. In mouse model of tuberculous lung infection, intranasal inoculations mice an IgA monoclonal antibody (mAb) the α‐crystallin antigen Mycobacterium tuberculosis reduced up to 10‐fold bacterial counts at nine days after either aerosol‐ or challenge. This effect involved synergism between mAb shortly before and 3 infection. Monomeric colony‐forming unit...
The low-affinity immunoglobulin E (IgE) receptor, CD23 (FcεRII), binds both IgE and CD21 and, through these interactions, regulates the synthesis of IgE, antibody isotype that mediates allergic response. We have determined three-dimensional structure C-type lectin domain in solution by nuclear magnetic resonance spectroscopy. An analysis concentration-dependent chemical shift perturbations allowed us to identify residues engaged self-association trimeric state, whereas ligand-induced changes...
Recombinant Secretory IgA (SIgA) complexes have the potential to improve antibody-based passive immunotherapeutic approaches combat many mucosal pathogens. In this report, we describe expression, purification and characterization of a human SIgA format broadly neutralizing anti-HIV monoclonal antibody (mAb) 2G12, using both transgenic tobacco plants transient expression in Nicotiana benthamiana as hosts (P2G12 SIgA). The resulting heterodecameric accumulated intracellular compartments leaf...
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...
Abstract Tuberculosis (TB) is the most lethal infection among infectious diseases. The specific aim of this study was to establish panels serum protein biomarkers representative active TB patients and their household contacts who were either infected (LTBI) or uninfected (EMI-TB Discovery Cohort, Pontevedra Region, Spain). A TMT (Tamdem mass tags) 10plex-based quantitative proteomics performed in quintuplicate containing a total 15 individual samples per group. Peptides analyzed an...
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...
Buruli ulcer (BU) disease, a neglected necrotizing tropical skin infection caused by Mycobacterium ulcerans , is the third most common mycobacterial disease after tuberculosis and leprosy. Infections mostly occur in remote, rural areas of Central West Africa, but also Australia, Japan Papua New Guinea. There currently no vaccine against all previous attempts using closely related bacteria subunit proteins have been partially successful only. Here, we tested mice composite formulation...
The influence of Th2 cytokines in tuberculosis has been a matter dispute. Here we report that IL-4 profound regulatory effect on the infection BALB/c mice with Mycobacterium tuberculosis. Depletion neutralizing mAb caused only evanescent reduction lung infection, but when combined i.n. inoculations IgA anti-mycobacterial alpha-crystallin and mouse rIFN-gamma, observed 40-fold bacterial counts lungs at 3 wks following (p<0.001). In genetically deficient IL-4-/- mice, both spleen was...
Summary Intranasal inoculation of mice with monoclonal IgA against the α-crystallin (acr1) antigen can diminish tuberculous infection in lungs. As this effect has been observed only over a short-term, we investigated if it could be extended by IFNγ 3 days before infection, and further coinoculations IgA, at 2 h 7 after aerosol Mycobacterium tuberculosis H37Rv. This treatment reduced lung 4 weeks more than either or alone (i.e. 17-fold, from 4·2 × 107 to 2·5 106 CFU, P = 0·006), accompanied...
Mucosal boosting of BCG-immunised individuals with a subunit tuberculosis (TB) vaccine would be highly desirable, considering that the lungs are principal port entry for Mycobacterium (MTB) and site primary infection reactivation. However, main roadblock TB development is lack suitable adjuvants could induce robust local systemic immune responses. Here, we describe novel delivery system was designed to mimic, in part, MTB pathogen itself. The surface yellow carnauba wax nanoparticles coated...
Summary Progress with protein‐based tuberculosis ( TB ) vaccines has been limited by poor availability of adjuvants suitable for human application. Here, we developed and tested a novel approach to molecular engineering adjuvanticity that circumvents the need exogenous adjuvants. Thus, generated expressed in transgenic tobacco plants recombinant immune complexes RIC s) incorporating early secreted Ag85B latency‐associated Acr antigen Mycobacterium , genetically fused as single polypeptide...
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...
A better understanding of the response against Tuberculosis (TB) infection is required to accurately identify individuals with an active or a latent TB (LTBI) and also those LTBI patients at higher risk developing TB. In this work, we have used information obtained from studying gene expression profile their infected –LTBI- uninfected –NoTBI- contacts, recruited in Spain Mozambique, build class-prediction model that identifies profile. Following approach, identified several genes metabolic...
ABSTRACT Needle-free, mucosal immunization is a highly desirable strategy for vaccination against many pathogens, especially those entering through the respiratory mucosa, such as Mycobacterium tuberculosis . Unfortunately, (TB) impeded by lack of suitable adjuvants and/or delivery platforms that could induce protective immune response in humans. Here, we report on novel biotechnological approach TB overcomes some current limitations. This achieved coating antigens onto surface inert...