IQUR Ltd | Date: 2015-02-18
The invention provides a protein comprising hepatitis B core antigen (HBcAg) with a sugar attached to an e1 loop. The protein may comprise a first and a second copy of HBcAg in tandem, wherein one or both copies of HBcAg has a sugar attached to the e1 loop. The first copy may have a sugar attached to the e1 loop and the second copy may comprise a peptide epitope in the e1 loop. The protein may be used to induce an immune response against the sugar and hence act as a vaccine.
Khoo E.Y.H.,National University of Singapore |
Stevenson M.C.,University of Nottingham |
Leverton E.,University of Nottingham |
Cross R.,IQur Ltd |
And 8 more authors.
Digestive Diseases and Sciences | Year: 2012
Background: Hyperalimentation for 4 weeks is associated with raised liver enzymes and liver fat content (LFC), which are two common features found in individuals with diabetes. Aim: We evaluated the effect of two mixed meal challenges on LFC, liver enzymes and serum bio-markers of liver injury and fibrosis in 16 healthy volunteers (HV) and subjects with type 2 diabetes (T2DM). Methods: Subjects (HV: 9 male, 7 female, aged 57.9 ± 1.7 years, body mass index (BMI) 27.1 kg/m2; and T2DM: 11 male, 5 female, aged 62.1 ± 1.3 years, BMI 28.0 ± 0.4 kg/m2) consumed two meals at 1 h (884 kcal) and at 6 h (1,096 kcal). LFC determined by 1H magnetic resonance spectroscopy, serum levels of liver enzymes, hyaluronic acid (HA), procollagen III N-terminal peptide (P3NP) and tissue inhibitor metalloproteinase-1 (TIMP-1) were estimated at time 0 (fasting) and 9 h (postprandial). Results: Fasting LFC was higher in the T2DM group 7.6 % (4.9, 15.4) [median (inter-quartile range)] than in the HV group 2.3 % (0.8, 5.1) (p<0.05) while levels of HA, P3NP and TIMP-1 were similar. Following the meal challenge there was no significant change in LFC. Subjects with T2DM had higher post-prandial rise in alanine transaminase (ALT) (p = 0.014), serum HA (p = 0.007) and P3NP (p = 0.015) compared with HV. Fasting LFC correlated with a greater post-prandial increase in P3NP levels in all subjects (Pearson correlation r = 0.53, p = 0.001). Conclusions: In subjects with T2DM, a mixed meal challenge is associated with a significant elevation in the serum levels of ALT, HA and P3NP without significant changes in LFC. These markers should be performed in the fasted state. © Springer Science+Business Media, LLC 2012.
PubMed | University of Groningen, European Vaccine Initiative EEIG, iQur Ltd, Erasmus University Rotterdam and The Institute of Virology and Immunology IVI
Type: Review | Journal: Vaccine | Year: 2016
Due to influenza viruses continuously displaying antigenic variation, current seasonal influenza vaccines must be updated annually to include the latest predicted strains. Despite all the efforts put into vaccine strain selection, vaccine production, testing, and administration, the protective efficacy of seasonal influenza vaccines is greatly reduced when predicted vaccine strains antigenically mismatch with the actual circulating strains. Moreover, preparing for a pandemic outbreak is a challenge, because it is unpredictable which strain will cause the next pandemic. The European Commission has funded five consortia on influenza vaccine development under the Seventh Framework Programme for Research and Technological Development (FP7) in 2013. The call of the EU aimed at developing broadly protective influenza vaccines. Here we review the scientific strategies used by the different consortia with respect to antigen selection, vaccine delivery system, and formulation. The issues related to the development of novel influenza vaccines are discussed.
Trepo E.,Free University of Colombia |
Potthoff A.,Medizinische Hochschule |
Pradat P.,Hospices Civils de Lyon |
Pradat P.,French Institute of Health and Medical Research |
And 19 more authors.
Journal of Hepatology | Year: 2011
Background & Aims: Fibrosis progression in patients with chronic hepatitis C (CHC) is highly variable. A Cirrhosis Risk Score (CRS) based on seven genetic variants has been recently developed for identifying patients at risk for cirrhosis. The objective of this study was to assess the role of the CRS for the early prediction of fibrosis progression in CHC patients with mild liver fibrosis. In addition, we evaluated the potential benefit, for prediction accuracy, of a recently described non-invasive fibrosis staging assay, the Enhanced Liver Fibrosis (ELF) test. Methods: Two separate cohorts of HCV patients (Brussels, Belgium/Hannover, Germany) were retrospectively analyzed. Only patients with a fibrosis Ishak or METAVIR score of F0-F1 at baseline were included. Patients were classified as progressors if they showed an increase ≥2 fibrosis stages at the second histological evaluation after a follow-up ≥5 years. The CRS was calculated locally. Genotyping was performed by PCR and oligonucleotide ligation with the resulting signal detected with a Luminex® 200TM and computer analysis. Results: In Brussels, 12/25 patients progressed (48%); similarly in Hannover, 16/31 (52%) patients progressed. In both sample sets, the CRS was significantly associated with fibrosis progression (p = 0.050 in Brussels; p = 0.018 in Hannover). The ELF test was only a significant predictor in Hannover (p = 0.015). In multivariate analysis the CRS remained the only variable associated with fibrosis progression (odds-ratio = 2.23, 95%CI 1.21-4.11 p = 0.01). Conclusions: Although conducted on a limited number of patients, this study in two independent centres confirms that the CRS predicts fibrosis progression in initially mild CHC. © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.3.0-1 | Award Amount: 5.06M | Year: 2013
FLUTCORE will develop a novel universal influenza A virus (IAV) vaccine based on the tandem core vaccine platform. Recent influenza pandemics have emphasized the urgent need for better vaccines that are reactive with multiple IAV subtypes and that are no longer dependent on intimate knowledge of the prevalent virus. We propose to replace the existing seasonal IAV vaccine with a virus like particle (VLP) carrying several invariant universal influenza antigens. Previous attempts to use these targets have failed due to the poor antigen expression and immunogenicity. The highly immunogenic tandem core system overcomes this limitation. Specifically, we propose to develop a VLP carrying two or more invariant influenza antigens, express these in yeast and then examine immunogenicity in mice. The vaccine will be further tested in the rigorous ferret system before being scaled up for manufacture. An optimal clone will then be transferred to an accredited contract manufacturer for production. A phase I clinical trial will be carried out once pre-clinical toxicology has been successfully completed. Our consortium will examine the immune responses in both animals and humans thoroughly to ensure that the vaccine candidate chosen can produce a protective IAV immune response in all individuals. To achieve these objectives, our proposal builds upon the complementary expertise of seven high-performing partners representing four European countries, with world leadership in HBV core biology, immunological analysis, commercial manufacture and influenza clinical trials, making our consortium ideally positioned to develop the vaccine and to take it from bench to bedside. The leading role of SMEs in the consortium will ensure that the technology developed by FLUTCORE will generate highly marketable products, offering both improved patient protection and long-term cost savings for health care in Europe once annual influenza vaccines are replaced.
PubMed | University of Leeds, University of Oxford, John Innes Center and iQur Ltd
Type: Journal Article | Journal: PloS one | Year: 2015
The core protein of the hepatitis B virus, HBcAg, assembles into highly immunogenic virus-like particles (HBc VLPs) when expressed in a variety of heterologous systems. Specifically, the major insertion region (MIR) on the HBcAg protein allows the insertion of foreign sequences, which are then exposed on the tips of surface spike structures on the outside of the assembled particle. Here, we present a novel strategy which aids the display of whole proteins on the surface of HBc particles. This strategy, named tandem core, is based on the production of the HBcAg dimer as a single polypeptide chain by tandem fusion of two HBcAg open reading frames. This allows the insertion of large heterologous sequences in only one of the two MIRs in each spike, without compromising VLP formation. We present the use of tandem core technology in both plant and bacterial expression systems. The results show that tandem core particles can be produced with unmodified MIRs, or with one MIR in each tandem dimer modified to contain the entire sequence of GFP or of a camelid nanobody. Both inserted proteins are correctly folded and the nanobody fused to the surface of the tandem core particle (which we name tandibody) retains the ability to bind to its cognate antigen. This technology paves the way for the display of natively folded proteins on the surface of HBc particles either through direct fusion or through non-covalent attachment via a nanobody.
Parkes J.,University of Southampton |
Guha I.N.,University of Nottingham |
Roderick P.,University of Southampton |
Harris S.,University of Southampton |
And 7 more authors.
Journal of Viral Hepatitis | Year: 2011
Assessment of liver fibrosis is important in determining prognosis and evaluating interventions. Due to limitations of accuracy and patient hazard of liver biopsy, non-invasive methods have been sought to provide information on liver fibrosis, including the European liver fibrosis (ELF) test, shown to have good diagnostic accuracy for the detection of moderate and severe fibrosis. Access to independent cohorts of patients has provided an opportunity to explore if this test could be simplified. This paper reports the simplification of the ELF test and its ability to identity severity of liver fibrosis in external validation studies in patients with chronic hepatitis C (CHC). Paired biopsy and serum samples from 347 naïve patients with CHC in three independent cohorts were analysed. Diagnostic performance characteristics were derived (AUROC, sensitivity and specificity, predictive values), and clinical utility modelling performed to determine the proportion of biopsies that could have been avoided if ELF test was used in this patient group. It was possible to simplify the original ELF test without loss of performance and the new algorithm is reported. The simplified ELF test was able to predict severe fibrosis [pooled AUROC of 0.85 (95% CI 0.81-0.89)] and using clinical utility modelling to predict severe fibrosis (Ishak stages 4-6; METAVIR stages 3 and 4) 81% of biopsies could have been avoided (65% correctly). Issues of spectrum effect in diagnostic test evaluations are discussed. In chronic hepatitis C a simplified ELF test can detect severe liver fibrosis with good accuracy. © 2010 Blackwell Publishing Ltd.