Julian D. Harris
Royal Holloway, University of London
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Featured researches published by Julian D. Harris.
Proceedings of the National Academy of Sciences of the United States of America | 2009
Adel Benlahrech; Julian D. Harris; Andrea Meiser; Timos Papagatsias; Julia Hornig; Peter Hayes; André Lieber; Takis Athanasopoulos; Veronique Bachy; Eszter Csomor; Rod Daniels; Kerry D. Fisher; Frances Gotch; Len Seymour; Km Logan; Romina Barbagallo; Linda Klavinskis; George Dickson; Steven Patterson
In the recently halted HIV type 1 (HIV-1) vaccine STEP trial, individuals that were seropositive for adenovirus serotype 5 (Ad5) showed increased rates of HIV-1 infection on vaccination with an Ad5 vaccine. We propose that this was due to activation and expansion of Ad5-specific mucosal-homing memory CD4 T cells. To test this hypothesis, Ad5 and Ad11 antibody titers were measured in 20 healthy volunteers. Dendritic cells (DCs) from these individuals were pulsed with replication defective Ad5 or Ad11 and co-cultured with autologous lymphocytes. Cytokine profiles, proliferative capacity, mucosal migration potential, and susceptibility to HIV infection of the adenovirus-stimulated memory CD4 T cells were measured. Stimulation of T cells from healthy Ad5-seropositive but Ad11-seronegative individuals with Ad5, or serologically distinct Ad11 vectors induced preferential expansion of adenovirus memory CD4 T cells expressing α4β7 integrins and CCR9, indicating a mucosal-homing phenotype. CD4 T-cell proliferation and IFN-γ production in response to Ad stimulation correlated with Ad5 antibody titers. However, Ad5 serostatus did not correlate with total cytokine production upon challenge with Ad5 or Ad11. Expanded Ad5 and Ad11 memory CD4 T cells showed an increase in CCR5 expression and higher susceptibility to infection by R5 tropic HIV-1. This suggests that adenoviral-based vaccination against HIV-1 in individuals with preexisting immunity against Ad5 results in preferential expansion of HIV-susceptible activated CD4 T cells that home to mucosal tissues, increases the number of virus targets, and leads to a higher susceptibility to HIV acquisition.
Gene Therapy | 2002
Julian D. Harris; Silke Schepelmann; Takis Athanasopoulos; Ian R. Graham; Anita K. Stannard; Z Mohri; Vanessa J. Hill; David G. Hassall; James S. Owen; George Dickson
Apolipoprotein E (apoE) is a multifunctional plasma glycoprotein involved in lipoprotein metabolism and a range of cell signalling phenomena. ApoE-deficient (apoE-/-) mice exhibit severe hypercholesterolaemia and are an excellent model of human atherosclerosis. ApoE somatic gene transfer and bone marrow transplantation in apoE-/- mice results in reversal of hypercholesterolaemia, inhibition of atherogenesis and regression of atherosclerotic plaque density. Replication defective adeno-associated virus vectors (rAAVs) are an attractive system currently in clinical trial for muscle-based heterologous gene therapy to express secreted recombinant plasma proteins. Here we have applied rAAV transduction of skeletal muscle to express wild-type (ɛ3) and a defective receptor-binding mutant (ɛ2) human apoE transgene in apoE-/- mice. In treated animals, apoE mRNA was present in transduced muscles and, although plasma levels of recombinant apoE fell below the detection levels of our ELISA (ie <10 ng/ml), circulating antibodies to human apoE and rAAV were induced. Up to 3 months after a single administration of rAAV/apoE3, a significant reduction in atherosclerotic plaque density in aortas of treated animals was observed (approximately 30%), indicating that low-level rAAV-mediated apoE3 expression from skeletal muscle can retard atherosclerotic progression in this well-defined genetic model.
European Journal of Immunology | 2005
George Rozis; Shamika de Silva; Adel Benlahrech; Timos Papagatsias; Julian D. Harris; Frances Gotch; George Dickson; Steven Patterson
Vaccines against viruses need to target dendritic cells (DC) and stimulate mucosal immunity. Most vaccine studies have focussed on monocyte‐derived or dermal DC (dDC) but recent evidence suggests that Langerhans cells (LC) may stimulate mucosal immunity more effectively. New chimeric adenovirus vectors expressing fibre protein from group B adenoviruses (rAd5/11), which utilise CD46 rather than the Coxsackie adenovirus receptor (CAR), have been developed as vaccines to improve transduction and overcome problems of pre‐existing vector immunity. Transduction of LC and dDC by rAd5/11 and standard rAd5 expressing green fluorescent protein (GFP) showed that both DC types were more efficiently transduced by rAd5/11 than by rAd5. Although expression of CD46 and the integrins αvβ3 and αvβ5, which recognise the adenovirus penton base and mediate virus internalisation, was similar in LC and dDC, LC expressed higher levels of GFP. Transduction by electroporation of plasmid also resulted in higher GFP expression in LC, suggesting differences between the two DC populations at a post‐entry stage. Transduction with either vector did not induce maturation of LC or dDC and did not affect their ability to stimulate T cells. These findings suggest that vaccine strategies that target LC with adenovirus vectors may be worthy of exploration.
Journal of Cerebral Blood Flow and Metabolism | 2007
Barry W. McColl; Ailsa McGregor; Andrew Wong; Julian D. Harris; Andrea Amalfitano; Sandra Magnoni; Andrew H. Baker; George Dickson; Karen Horsburgh
Apolipoprotein E (apoE, protein; APOE, gene) is the major lipid-transport protein in the brain and plays an important role in modulating the outcome and regenerative processes after acute brain injury. The aim of the present study was to determine if gene transfer of the ε3 form of APOE improves outcome in a murine model of transient focal cerebral ischaemia. Mice received an intrastriatal injection of vehicle, a second-generation adenoviral vector containing the green fluorescent protein gene (Ad-GFP) or a vector containing the APOE ε3 gene (Ad-APOE) 3 days before 60 mins focal ischaemia. Green fluorescent protein expression was observed in cells throughout the striatum and subcortical white matter indicating successful gene transfer and expression. ApoE levels in the brain were significantly increased after Ad-APOE compared with Ad-GFP or vehicle treatment. Ad-APOE treatment reduced the volume of ischaemic damage by 50% compared with Ad-GFP or vehicle treatment (13±3 versus 29±4 versus 27±5 mm3). The extent of postischaemic apoE immunoreactivity was enhanced in Ad-APOE compared with Ad-GFP or vehicle treated mice. These results show the ability of APOE gene transfer to markedly improve outcome after cerebral ischaemia and suggest that modulating apoE levels may be a potential strategy in human stroke therapy.
Retrovirology | 2009
Adel Benlahrech; Julian D. Harris; Andrea Meiser; Timos Papagatsias; Julia Hornig; Peter Hayes; André Lieber; Takis Athanasopoulos; Veronique Bachy; Rod Daniels; Kerry D. Fisher; Frances Gotch; Linda Klavinskis; Len Seymour; Km Logan; Romina Barbagallo; George Dickson; Steven Patterson
Open Access Oral presentation OA07-02. Adenovirus vectors induce expansion of memory CD4 T cells with a mucosal homing phenotype that are readily susceptible to HIV-1 infection A Benlahrech*1, J Harris2, A Meiser1, T Papagatsias1, J Hornig1, P Hayes1, A Lieber3, T Athanasopoulos2, V Bachy4, R Daniels5, K Fisher6, F Gotch1, L Klavinskis4, L Seymour6, K Logan1, R Barbagallo1, G Dickson2 and S Patterson1
Human Molecular Genetics | 2002
Julian D. Harris; Ian R. Graham; Silke Schepelmann; Anita K. Stannard; Michael L. Roberts; Bradley L. Hodges; Vanessa J. Hill; Andrea Amalfitano; David G. Hassall; James S. Owen; George Dickson
Biochimica et Biophysica Acta | 2005
Aristides D. Tagalakis; Ivan Diakonov; Ian R. Graham; Karen A. Heald; Julian D. Harris; Jane V. Mulcahy; George Dickson; James S. Owen
Methods in molecular medicine | 2003
Julian D. Harris; Stuart G. Beattie; J. George Dickson
in Vivo | 2009
Julian D. Harris; Michael L. Roberts; Dhayaneethie Perumal; Ian R. Graham; Steve Patterson; George Dickson
Retrovirology | 2009
Timos Papagatsias; Takis Athanasopoulos; Andrea Meiser; Adel Benlahrech; Fusheng Li; S Self; Julian D. Harris; N Roesen; Veronique Bachy; Linda Klavinskis; Kerry D. Fisher; S Oh; S Kwong; Rod Daniels; Len Seymour; George Dickson; Steven Patterson