A5102536783- Hepatitis C virus research
- Hepatitis B Virus Studies
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Cytomegalovirus and herpesvirus research
- SARS-CoV-2 and COVID-19 Research
- Bacteriophages and microbial interactions
- Respiratory viral infections research
- Viral gastroenteritis research and epidemiology
- HIV Research and Treatment
- Virus-based gene therapy research
- COVID-19 Clinical Research Studies
- Long-Term Effects of COVID-19
- Liver Disease Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- Immune Response and Inflammation
- Chemokine receptors and signaling
- Molecular Biology Techniques and Applications
- Blood groups and transfusion
- Photodynamic Therapy Research Studies
- Neuroendocrine Tumor Research Advances
- Nanoplatforms for cancer theranostics
- Immune responses and vaccinations
- Glycosylation and Glycoproteins Research
University of Oxford
2013-2025
Medawar Building for Pathogen Research
2011-2023
Freie Universität Berlin
2019
Humboldt-Universität zu Berlin
2019
Jenner Institute
2004-2009
Imperial College London
2005
St George's, University of London
2005
Mary Lyon Centre at MRC Harwell
1998
CD161(++) CD8(+) T cells represent a novel subset that is dominated in adult peripheral blood by mucosal-associated invariant (MAIT) cells, as defined the expression of variable-α chain 7.2 (Vα7.2)-Jα33 TCR, and IL-18Rα. Stimulation with IL-18+IL-12 known to induce IFN-γ both NK and, more limited extent, cells. Here, we show T-cell population primary triggered this mechanism. Both Vα7.2(+) Vα7.2(-) subsets responded IL-12+IL-18 stimulation, demonstrating response was not restricted MAIT but...
Abstract Mucosal-associated invariant T (MAIT) cells are abundant in humans and recognize bacterial ligands. Here, we demonstrate that MAIT also activated during human viral infections vivo . activation was observed infection with dengue virus, hepatitis C virus influenza virus. This activation—driving cytokine release Granzyme B upregulation—is TCR-independent but dependent on IL-18 synergy IL-12, IL-15 and/or interferon-α/β. levels cell correlate disease severity acute infection....
Extension of the interval between vaccine doses for BNT162b2 mRNA was introduced in United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed study healthcare workers. The first dose induced protection from infection circulating alpha (B.1.1.7) variant over several weeks. In substudy 589 individuals, show that induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses sustained...
Abstract Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with from those cross-reactive immunity to other coronaviruses. Here we show a range assays that differentially capture immune function characterise responses. Strong ex vivo ELISpot and proliferation multiple antigens (including M, NP ORF3) are found in 168 PCR-confirmed volunteers, but rare 119 uninfected volunteers. Highly exposed seronegative healthcare workers recent...
Memory T cells can be divided into central-memory (T(CM)) and effector-memory (T(EM)) cells, which differ in their functional properties. Although both subpopulations persist long term, it is not known whether they are maintained by similar mechanisms. We used vivo labeling with deuterated glucose to measure the turnover of CD4(+) healthy humans. The CD45R0(+)CCR7(-) T(EM) subpopulation was shown have a rapid proliferation rate 4.7% per day compared 1.5% for CD45R0(+)CCR7(+) T(CM) cells;...
Advancing interventions to tackle the huge global burden of hepatitis B virus (HBV) infection depends on improved insights into epidemiology, transmission, within-host diversity, drug resistance and pathogenesis, all which can be advanced through large-scale generation full-length genome data. Here we describe advances a protocol that exploits circular HBV structure, using isothermal rolling-circle amplification enrich DNA, generating concatemeric amplicons containing multiple successive...
Respiratory syncytial virus (RSV) infection causes respiratory disease throughout life, with infants and the elderly at risk of severe death. RSV001 is a phase 1 (first-in-man), open-label, dose-escalation, clinical trial novel genetic viral-vectored vaccine candidates PanAd3-RSV modified vaccinia Ankara (MVA)-RSV. The objective to characterise (primary objective) safety (secondary immunogenicity these vaccines in healthy younger older adults.
Respiratory syncytial virus (RSV) disease is a major cause of infant morbidity and mortality. This Phase I, randomized, observer-blind, placebo- active-controlled study evaluated an investigational vaccine against RSV (ChAd155-RSV) using the viral vector chimpanzee-adenovirus-155, encoding fusion (F), nucleocapsid, transcription antitermination proteins.Healthy 18-45-year-old adults received ChAd155-RSV, placebo, or active control (Bexsero) at Days (D) 0 30. An escalation from low dose (5 ×...
Convincing correlates of protective immunity against tuberculosis have been elusive. In BALB/c mice, intranasal immunization with a replication-deficient recombinant adenovirus expressing Mycobacterium antigen 85A (adenovirus-85A) induces lower respiratory tract pulmonary challenge tuberculosis, while intradermal adenovirus-85A does not. Here we report that expression the chemokine receptor CXCR6 on lung CD8 T lymphocytes, which is maintained for at least 3 months. CXCR6-positive...
Following exposure to vaccines, antigen-specific CD8+ T cell responses develop as long-term memory pools. Vaccine strategies based on adenoviral vectors, e.g., those developed for HCV, are able induce and sustain substantial populations. How such populations evolve following vaccination remains be defined at a transcriptional level. We addressed the regulation of divergent pools induced by an adenovector encoding model antigen (beta-galactosidase). observe profiles that mimic infection with...
Abstract Hepatitis B virus (HBV) whole genome sequencing (WGS) is currently limited as the DNA viral loads (VL) of many clinical samples are below threshold required to generate full genomes using current methods. We developed two pan-genotypic enrichment methods, probe-based capture and tiled amplicon PCR (HEP-TILE) for HBV WGS. demonstrate mock that both methods (genotypes A-J). Using samples, we HEP-TILE amplification successfully amplifies at lowest VL tested (30 IU/ml), products can be...
CD8(+) T cell memory inflation, first described in murine CMV (MCMV) infection, is characterized by the accumulation of high-frequency, functional Ag-specific pools with an effector-memory phenotype and enrichment peripheral organs. Although persistence Ag considered essential, rules underpinning inflation are still unclear. The MCMV model is, however, complicated virus's low-level stochastic reactivation. We developed a new based on β-galactosidase (βgal)-recombinant adenovirus vector....
Background BCG, the only licensed vaccine against tuberculosis, provides some protection disseminated disease in infants but has little effect on prevention of adult pulmonary disease. Newer parenteral immunization prime boost regimes may provide improved experimental animal models are unproven man so that there remains a need for new and strategies. Methods Findings Mice were immunized parenterally, intranasally or simultaneously by both routes with BCG recombinant mycobacterial antigens...
Background and Aims Induction of functional helper CD4 + T cells is the hallmark a protective immune response against hepatitis C virus (HCV), associated with spontaneous viral clearance. Heterologous prime/boost vectored vaccination has demonstrated induction broad polyfunctional HCV‐specific CD8 in healthy volunteers; however, much less known about T‐cell subsets following vaccination. Approach Results We analyzed populations using major histocompatibility complex class II tetramers...
Abstract A major issue in identification of protective T cell responses against SARS-CoV-2 lies distinguishing people infected with from those cross-reactive immunity generated by exposure to other coronaviruses. We characterised immune 168 PCR-confirmed subjects and 118 seronegative without known using a range assays that differentially capture function. Strong ex vivo ELISpot proliferation multiple antigens (including M, NP ORF3) were found who had been but rare pre-pandemic unexposed...
ABSTRACT Hepatitis B Virus (HBV) genome sequencing can be used to provide more complete genetic information at the population and individual level shed light on limitations of current interventions, inform new strategies for elimination. HBV is challenging due partially dsDNA genome, high diversity, low viral loads presence large amounts host material in clinical samples. Here we describe design use a pan-genotypic panel 74 specific capture-probes nuclease treatment improving efficiency. We...
CD4+ T-cell loss is the hallmark of HIV-1 infection. CD4 counts fall more rapidly in advanced disease when CCR5-tropic viral strains tend to be replaced by X4-tropic viruses. We hypothesized: (i) that early dominance viruses results from faster turnover rates CCR5+ cells, and (ii) exert greater pathogenicity preferentially increasing within CXCR4+ compartment. To test these hypotheses we measured vivo subpopulations sorted chemokine receptor expression, using deuterium-glucose labeling....
Hepatitis B virus (HBV) whole genome sequencing (WGS) is currently limited as the DNA viral loads (VL) of many clinical samples are below threshold required to generate full genomes using current methods. We developed two pan-genotypic enrichment methods, probe-based capture and tiled amplicon PCR (HEP-TILE) for HBV WGS. demonstrate mock that both methods (genotypes A-J). Using samples, we HEP-TILE amplification successfully amplifies at lowest VL tested (30 IU/ml), products can be sequenced...
Abstract Confocal fluorescence microscopy, using a newly constructed laser line‐scanning confocal microscope, was applied to an investigation of the early stages photoinduced destruction V79–4Chinese hamster fibroblasts aluminum and zinc phthalocyanines as photosensitize. Results obtained in this work show that phthalocyanines, once internalized, localize perinuclear sites are disrupted upon light exposure resulting redistribution. The combination laser‐line scanning with charge‐coupled...
The efficacies of many new T cell vaccines rely on generating large populations long-lived pathogen-specific effector memory CD8 cells. However, it is now increasingly recognized that prior infection history impacts the host immune response. Additionally, order in which these infections are acquired could have a major effect. Exploiting ability to generate sustained (i.e. inflationary) from murine cytomegalovirus (MCMV) and human Adenovirus-subtype (AdHu5) 5-beta-galactosidase (Ad-lacZ)...
<ns4:p><ns4:bold>Background</ns4:bold>: Persistent viruses such as murine cytomegalovirus (MCMV) and adenovirus-based vaccines induce strong, sustained CD8<ns4:sup>+</ns4:sup> T-cell responses, described memory “inflation”. These retain functionality, home to peripheral organs are associated with a distinct transcriptional program.</ns4:p><ns4:p> <ns4:bold>Methods</ns4:bold>: To further define the nature of mechanisms underpinning inflation at different sites we used single-cell RNA...