A5067817899- HIV Research and Treatment
- Immune Cell Function and Interaction
- vaccines and immunoinformatics approaches
- HIV/AIDS drug development and treatment
- Immunotherapy and Immune Responses
- HIV/AIDS Research and Interventions
- T-cell and B-cell Immunology
- Hepatitis B Virus Studies
- HIV-related health complications and treatments
- Hepatitis C virus research
- Virus-based gene therapy research
- Cytomegalovirus and herpesvirus research
- Tuberculosis Research and Epidemiology
- Pneumocystis jirovecii pneumonia detection and treatment
- Herpesvirus Infections and Treatments
- Cardiovascular Disease and Adiposity
- Cervical Cancer and HPV Research
- Reproductive tract infections research
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- Liver Disease Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- CAR-T cell therapy research
- Respiratory viral infections research
- COVID-19 Clinical Research Studies
Immunocore (United Kingdom)
2018-2024
University of Oxford
2014-2023
Jenner Institute
2014-2023
Oxford BioMedica (United Kingdom)
2012-2022
National Institute for Health Research
2015-2021
John Radcliffe Hospital
2006-2017
Churchill Hospital
2004-2017
St Vincent's Hospital
2013-2016
Groote Schuur Hospital
2016
University of Cape Town
2016
BackgroundOne of the big roadblocks in development HIV-1/AIDS vaccines is enormous diversity HIV-1, which could limit value any HIV-1 vaccine candidate currently under test.Methodology and FindingsTo address variation, we designed a novel T cell immunogen, designated HIVCONSV, by assembling 14 most conserved regions proteome into one chimaeric protein. Each segment consensus sequence from four major clades A, B, C D, alternate to ensure equal clade coverage. The gene coding for HIVCONSV...
ABSTRACT A double-blind randomized phase I trial was conducted in human immunodeficiency virus type 1 (HIV-1)-negative subjects receiving vaccines vectored by plasmid DNA and modified vaccinia Ankara (MVA) expressing HIV-1 p24/p17 gag linked to a string of CD8 + T-cell epitopes. The had two groups. One group received either doses MVA.HIVA (2× MVA.HIVA) ( n = 8) or placebo placebo) 4). second 2× pTHr.HIVA followed one dose 3× In the pTHr.HIVA-MVA.HIVA group, HIV-1-specific responses peaked...
The immunogenicities of candidate DNA- and modified vaccinia virus Ankara (MVA)-vectored human immunodeficiency (HIV) vaccines were evaluated on their own in a prime-boost regimen phase I clinical trials healthy uninfected individuals the United Kingdom. Given current lack approaches capable inducing broad HIV-neutralizing antibodies, pTHr.HIVA DNA MVA.HIVA focus solely induction cell-mediated immunity. expressed common immunogen, HIVA, which consists consensus HIV-1 clade A Gag p24/p17...
Virus diversity and escape from immune responses are the biggest challenges to development of an effective vaccine against HIV-1. We hypothesized that T-cell vaccines targeting most conserved regions HIV-1 proteome, which common variants bear fitness costs when mutated, will generate effectors efficiently recognize kill virus-infected cells early enough after transmission potentially impact on replication do so more than whole protein-based vaccines. Here, we describe first-ever...
Background— HIV infection continues to be endemic worldwide. Although treatments are successful, it remains controversial whether patients receiving optimal therapy have structural, functional, or biochemical cardiac abnormalities that may underlie their increased morbidity and mortality. The purpose of this study was characterize myocardial in a contemporary group HIV-infected individuals undergoing combination antiretroviral therapy. Methods Results— Volunteers with who were age-matched...
Background— Patients with treated HIV infection have clear survival benefits although increased cardiac morbidity and mortality. Mechanisms of heart disease may be partly related to untreated chronic inflammation. Cardiovascular magnetic resonance imaging allows a comprehensive assessment myocardial structure, function, tissue characterization. We investigated, using cardiovascular resonance, subclinical inflammation in asymptomatic HIV-infected individuals. Methods Results— Myocardial...
None of the HIV T-cell vaccine candidates that have reached advanced clinical testing been able to induce protective T cell immunity. A major reason for these failures may suboptimal immunogen designs. To overcome this problem, we used a novel design approach is based on functional response data from more than 1,000 HIV-1 clade B and C infected individuals which aims direct most vulnerable sites HIV-1. Our identified 16 regions in Gag, Pol, Vif Nef were relatively conserved predominantly...
There is an urgent need to understand the nature of immune responses against SARS-CoV-2, inform risk-mitigation strategies for people living with HIV (PLWH). Here we show that majority PLWH ART suppressed viral load, mount a detectable adaptive response SARS-CoV-2. Humoral and SARS-CoV-2-specific T cell are comparable between HIV-positive negative subjects persist 5-7 months following predominately mild COVID-19 disease. Spike, Membrane Nucleoprotein most prominent, CD4 cells outnumbering...
All thymically selected T cells are inherently cross-reactive, yet many data indicate a fine specificity in antigen recognition, which enables virus escape from immune control by mutation infections such as the human immunodeficiency (HIV). To address this paradox, we analyzed of recognizing histocompatibility leukocyte (HLA)-A2–restricted, strongly immunodominant, HIV gag epitope (SLFNTVATL). The majority 171 variant peptides tested bound HLA-A2, but only one third were recognized....
The incorporation of the fatty acids in fish and olive oil into colonic mucosa patients with inflammatory bowel disease was examined during 12 weeks' dietary supplementation oils, influence on mucosal prostaglandin thromboxane generation measured. With a supplement 18 g daily, concentrations major polyunsaturated oil, eicosapentaenoic acid docosahexaenoic acid, were significantly raised lipids. first time these measured, after three supplementation, mean increases seven fold 1.5...
Abstract Zika virus (ZIKV) emerged on a global scale and no licensed vaccine ensures long-lasting anti-ZIKV immunity. Here we report the design comparative evaluation of four replication-deficient chimpanzee adenoviral (ChAdOx1) ZIKV candidates comprising addition or deletion precursor membrane (prM) envelope, with without its transmembrane domain (TM). A single, non-adjuvanted vaccination ChAdOx1 vaccines elicits suitable levels protective responses in mice challenged ZIKV. prME ∆TM...
Background. Rare human immunodeficiency virus type 1 (HIV-1)–infected individuals who maintain control of viremia without therapy show potent CD8+ T-cell–mediated suppression viral replication in vitro. Whether this is a determinant the rate disease progression viremic unknown. Methods. We measured inhibition heterologous HIV-1 isolate 50 HIV-1–seropositive adults with diverse rates. Linear mixed models were used to determine whether T-cell function could explain variation CD4+ decline....
Trial Design HIV-1 vaccine development has advanced slowly due to viral antigenic diversity, poor immunogenicity and recently, safety concerns associated with human adenovirus serotype-5 vectors. To tackle variation, we designed a unique T-cell immunogen HIVconsv from functionally conserved regions of the proteome, which were presented immune system using heterologous prime-boost combination plasmid DNA, non-replicating simian (chimpanzee) ChAdV-63 poxvirus, modified vaccinia virus Ankara. A...
Peptides presented by HLA-E, a molecule with very limited polymorphism, represent attractive targets for T cell receptor (TCR)-based immunotherapies to circumvent the limitations imposed high polymorphism of classical HLA genes in human population. Here, we describe TCR-based bispecific that potently and selectively binds HLA-E complex peptide encoded inhA gene Mycobacterium tuberculosis (Mtb), causative agent humans. We reveal biophysical structural bases underpinning potency specificity...
Specific antibodies to HIV envelope that inactivate virus at the mucosal surfaces involved in sexual contact are of interest for design a vaccine against HIV-1. It has been suggested that, frequently HIV-exposed but uninfected individuals, HIV-specific antibody responses may exist and play role resistance HIV. This study investigated HIV-1 specific HIV-resistant sex workers west Africa.A group 26 exposed female commercial from Gambia, who have had repeated exposures HIV-2 were studied. We...
Recognition and eradication of infected cells by cytotoxic T lymphocytes is a key defense mechanism against intracellular pathogens. High‐throughput definition HLA class I‐associated immunopeptidomes mass spectrometry an increasingly important analytical tool to advance our understanding the induction T‐cell responses pathogens such as HIV‐1. We utilized liquid chromatography tandem workflow including de novo‐assisted database searching define immunopeptidome HIV‐1‐infected human cells. here...
To determine whether long-term HAART in chronic HIV-1 infection restores fully functional Mycobacterium tuberculosis (MTB)-specific CD4 T-cell responses.A cross-sectional study of HIV-1-seropositive subjects on continuous for over one year with cell counts greater than 300 cells/microl and undetectable viraemia, antiretroviral-naive individuals primary (PHI), healthy bacillus Calmette-Guérin-vaccinated low-risk controls.Purified protein derivative (PPD)-specific cytokine-secreting T cells...
Defining the components of an HIV immunogen that could induce effective CD8+ T cell responses is critical to vaccine development. We addressed this question by investigating viral targets cells potently inhibit replication in vitro, as highly predictive virus control vivo. observed broad and potent ex vivo cell-mediated inhibitory activity against a panel isolates among viremic controllers (VC, loads <5000 copies/ml), contrast unselected HIV-infected Vaccine trials Network (HVTN)...