A5046227670- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Immune responses and vaccinations
- Immunodeficiency and Autoimmune Disorders
- SARS-CoV-2 and COVID-19 Research
- HIV Research and Treatment
- Vaccine Coverage and Hesitancy
- Immune Cell Function and Interaction
- Diagnosis and treatment of tuberculosis
- COVID-19 Clinical Research Studies
- vaccines and immunoinformatics approaches
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- Cytomegalovirus and herpesvirus research
- Immune cells in cancer
- Virology and Viral Diseases
- Pneumocystis jirovecii pneumonia detection and treatment
- Cytokine Signaling Pathways and Interactions
- Infectious Diseases and Tuberculosis
- Parasites and Host Interactions
- COVID-19 epidemiological studies
- T-cell and B-cell Immunology
- Computational Drug Discovery Methods
- Multiple Sclerosis Research Studies
- Animal Disease Management and Epidemiology
University of Oxford
2016-2025
Jenner Institute
2015-2024
Wittenberg University
2022
University of Cape Town
2022
South African Tuberculosis Vaccine Initiative
2022
London School of Hygiene & Tropical Medicine
2022
MRC Weatherall Institute of Molecular Medicine
2009
Abstract Vaccines to protect against tuberculosis (TB) are urgently needed. We performed a case–control analysis identify immune correlates of TB disease risk in Bacille Calmette–Guerin (BCG) immunized infants from the MVA85A efficacy trial. Among 53 case and 205 matched controls, frequency activated HLA-DR + CD4 T cells associates with increased (OR=1.828, 95% CI=1.25–2.68, P =0.002, FDR=0.04, conditional logistic regression). In an independent study Mycobacterium -infected adolescents,...
HIV-1 accumulates mutations in and around reactive epitopes to escape recognition killing by CD8+ T cells. Measurements of time should therefore provide information on which parameters are most important for cell–mediated vivo control HIV-1. Primary HIV-1–specific cell responses were fully mapped 17 individuals, the virus escape, ranged from days years, was measured each epitope. While higher magnitude an individual response associated with more rapid significant measure its relative...
The relevance of antibodies (Abs) in the defense against Mycobacterium tuberculosis infection remains uncertain. We investigated role Abs to mycobacterial capsular polysaccharide arabinomannan (AM) and its oligosaccharide (OS) fragments humans.Sera obtained from 29 healthy adults before after primary or secondary bacillus Calmette-Guerin (BCG) vaccination were assessed for Ab responses AM via enzyme-linked immunosorbent assays, OS epitopes novel glycan microarrays. Effects prevaccination...
Mycobacterium tuberculosis is the main causative agent of tuberculosis. BCG, only licensed vaccine, provides inadequate protection against pulmonary Controlled human infection models are useful tools for vaccine development. We aimed to determine a safe dose aerosol-inhaled live-attenuated bovis BCG as surrogate M infection, then compare safety and tolerability established using intradermally administered BCG.
Despite the widespread use of Mycobacterium bovis BCG vaccine, there are more than 9 million new cases tuberculosis (TB) every year, and is an urgent need for better TB vaccines. vaccine candidates selected evaluation based in part on detection antigen-specific gamma interferon (IFN-γ) response. The measurement mycobacterial growth blood specimens obtained from subjects immunized with investigational vaccines may be a vitro correlate vivo efficacy. We performed clinical study 30 United...
The ratio of monocytes and lymphocytes (ML ratio) in peripheral blood is associated with tuberculosis malaria disease risk cancer cardiovascular outcomes. We studied anti-mycobacterial function the transcriptome relation to ML ratio. Mycobacterial growth inhibition assays whole or sorted were performed mycobacteria enumerated by liquid culture. Transcriptomes unstimulated CD14 + isolated magnetic bead sorting characterised microarray. Transcript expression was tested for association...
A SARS-CoV-2 controlled human infection model (CHIM) has been successfully established in seronegative individuals using a dose of 1×10
Immune activation is associated with increased risk of tuberculosis (TB) disease in infants. We performed a case-control analysis to identify drivers immune and risk. Among 49 infants who developed TB over the first 2 years life, 129 healthy matched controls, we found cytomegalovirus-stimulated (CMV-stimulated) IFN-γ response be CD8+ T cell (Spearman's rho, P = 6 × 10–8). A CMV-specific was also developing (conditional logistic regression; 0.043; OR, 2.2; 95% CI, 1.02–4.83) shorter time...
A major contribution to the burden of Tuberculosis (TB) comes from latent Mycobacterium tuberculosis infections (LTBI) becoming clinically active. TB and LTBI probably exist as a spectrum currently there are no correlates available identify individuals with most at risk developing active disease. We set out immune parameters associated ex vivo mycobacterial growth control among disease or define infection. used whole blood inhibition assay generate functional profile TB, uninfected controls....
Migrants and ethnic minorities in the UK have higher rates of tuberculosis (TB) compared with general population. Historically, much disparity incidence between UK-born migrant populations has been attributed to differential pathogen exposure, due migration from high-incidence regions transnational connections maintained TB endemic countries birth or origin. However, focusing solely on exposure fails address relatively high progression active disease observed some latently infected...
<ns4:p>Migrants and ethnic minorities in the UK have higher rates of tuberculosis (TB) compared with general population. Historically, much disparity incidence between UK-born migrant populations has been attributed to differential pathogen exposure, due migration from high-incidence regions transnational connections maintained TB endemic countries birth or origin. However, focusing solely on exposure fails address relatively high progression active disease observed some latently infected...
Development of an improved vaccine against tuberculosis (TB) is hindered by the lack a surrogate protection. Efficacy new TB vaccines in humans can only be evaluated expensive and time consuming efficacy trials within endemic areas. It critical that with greatest potential to protect are selected for these trials. Mycobacterial growth inhibition assays (MGIAs) have been developed hope in-vitro functional will correlate protection, which could aid selection best candidates. The present study...
Tuberculosis (TB) remains a leading global cause of morbidity and mortality an effective new vaccine is urgently needed. A major barrier to the rational development novel TB vaccines lack validated immune correlate or biomarker protection. Mycobacterial Growth Inhibition Assays (MGIAs) provide unbiased measure ability control mycobacterial growth in vitro, may represent functional However, biological relevance any potential can only be assessed by determining association with vivo protection...
Tuberculosis (TB) is a major global health problem and the only currently-licensed vaccine, BCG, inadequate. Many TB vaccine candidates are designed to be given as boost BCG; an understanding of BCG-induced immune response therefore critical, opportunity relate this circumstances where BCG does confer protection may direct design more efficacious vaccines. While T cell vaccination has been well-characterized, there paucity literature on humoral response. We demonstrate vaccine-mediated...
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...
Abstract The current vaccine against tuberculosis, live attenuated Mycobacterium bovis BCG, has variable efficacy, but development of an effective alternative is severely hampered by the lack immune correlate protection. There been a recent resurgence interest in functional vitro mycobacterial growth inhibition assays (MGIAs), which provide measure range different mechanisms and their interactions. We identified positive correlation between mean corpuscular haemoglobin BCG whole blood from...
Inducible nitric oxide synthase (iNOS) plays a crucial role in controlling growth of Mycobacterium tuberculosis (M.tb), presumably via (NO) mediated killing. Here we show that leukocyte-specific deficiency NO production, through targeted loss the iNOS cofactor tetrahydrobiopterin (BH4), results enhanced control M.tb infection; by contrast, renders mice susceptible to M.tb. By comparing two complementary NO-deficient models, Nos2