ORCID Profile
0000-0003-3598-7784
Current Organisations
University of Oxford Oxford Vaccine Group
,
University of Oxford
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Publisher: Public Library of Science (PLoS)
Date: 20-10-2020
Publisher: Public Library of Science (PLoS)
Date: 15-02-2013
Publisher: Rockefeller University Press
Date: 23-05-2016
DOI: 10.1084/JEM.20151025
Abstract: Enteric fever, caused by Salmonella enterica serovar Typhi, is an important public health problem in resource-limited settings and, despite decades of research, human responses to the infection are poorly understood. In 41 healthy adults experimentally infected with wild-type S. Typhi, we detected significant cytokine responses within 12 h of bacterial ingestion. These early responses did not correlate with subsequent clinical disease outcomes and likely indicate initial host–pathogen interactions in the gut mucosa. In participants developing enteric fever after oral infection, marked transcriptional and cytokine responses during acute disease reflected dominant type I/II interferon signatures, which were significantly associated with bacteremia. Using a murine and macrophage infection model, we validated the pivotal role of this response in the expression of proteins of the host tryptophan metabolism during Salmonella infection. Corresponding alterations in tryptophan catabolites with immunomodulatory properties in serum of participants with typhoid fever confirmed the activity of this pathway, and implicate a central role of host tryptophan metabolism in the pathogenesis of typhoid fever.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-03-2010
Publisher: Public Library of Science (PLoS)
Date: 26-12-2019
Publisher: American Society for Clinical Investigation
Date: 24-07-2023
Publisher: Public Library of Science (PLoS)
Date: 27-02-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-01-2009
Publisher: Springer Science and Business Media LLC
Date: 17-12-2020
Publisher: Springer Science and Business Media LLC
Date: 07-2019
Publisher: Elsevier BV
Date: 07-2011
Publisher: Elsevier BV
Date: 06-2010
Publisher: Wiley
Date: 31-08-2011
Publisher: Springer Science and Business Media LLC
Date: 21-05-2021
Publisher: Springer Science and Business Media LLC
Date: 17-12-2020
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.JIM.2013.03.001
Abstract: The capacity of CD8+ T cells to inhibit HIV-1 replication in vitro strongly correlates with virus control in vivo. Post-hoc evaluations of HIV-1 vaccine candidates suggest that this immunological parameter is a promising benchmark of vaccine efficacy. Large-scale analysis of CD8+ T cell antiviral activity requires a rapid, robust and economical assay for accurate quantification of HIV-1 infection in primary CD4+ T cells. Detection of intracellular HIV-1 p24 antigen (p24 Ag) by flow cytometry is one such method but it is thought to be less sensitive and quantitative than p24 Ag ELISA. We report that fixation and permeabilisation of HIV-infected cells using paraformaldehyde/50% methanol/Nonidet P-40 instead of a conventional paraformaldehyde/saponin-based protocol improved their detection across multiplicities of infection (MOI) ranging from 10(-2) to 8×10(-5), and by nearly two-fold (p<0.001) at the optimal MOI tested (10(-2)). The frequency of infected cells was strongly correlated with p24 Ag release during culture, thus validating its use as a measure of productive infection. We were also able to quantify infection with a panel of HIV-1 isolates representing the major clades. The protocol described here is rapid and cost-effective compared with ELISA and thus could be a useful component of immune monitoring of HIV-1 vaccines and interventions to reduce viral reservoirs.
Publisher: Springer Science and Business Media LLC
Date: 06-05-2021
Publisher: American Society for Microbiology
Date: 15-07-2013
DOI: 10.1128/JVI.00240-13
Abstract: Influenza virus defective interfering (DI) particles are naturally occurring noninfectious virions typically generated during in vitro serial passages in cell culture of the virus at a high multiplicity of infection. DI particles are recognized for the role they play in inhibiting viral replication and for the impact they have on the production of infectious virions. To date, influenza virus DI particles have been reported primarily as a phenomenon of cell culture and in experimentally infected embryonated chicken eggs. They have also been isolated from a respiratory infection of chickens. Using a sequencing approach, we characterize several subgenomic viral RNAs from human nasopharyngeal specimens infected with the influenza A(H1N1)pdm09 virus. The distribution of these in vivo -derived DI-like RNAs was similar to that of in vitro DIs, with the majority of the defective RNAs generated from the PB2 (segment 1) of the polymerase complex, followed by PB1 and PA. The lengths of the in vivo -derived DI-like segments also are similar to those of known in vitro DIs, and the in vivo -derived DI-like segments share internal deletions of the same segments. The presence of identical DI-like RNAs in patients linked by direct contact is compatible with transmission between them. The functional role of DI-like RNAs in natural infections remains to be established.
Publisher: Springer Science and Business Media LLC
Date: 08-07-2013
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Brian Angus.