DOCSLIB.ORG

Immunomodulatory Effects of the Hepatitis C Virus (HCV) Core Protein

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Immunomodulatory Effects of the Hepatitis C Virus (HCV) Core Protein Immunomodulatory Effects of the Hepatitis C Virus (HCV) Core Protein By Rachel Elizabeth Owen A thesis submitted for the degree of Doctor of Philosophy at the University of London September 2003 The Edward Jenner Institute for Vaccine Research University College London ProQuest Number: U642330 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest U642330 Published by ProQuest LLC(2015). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 Abstract Hepatitis C virus establishes a persistent infection in approximately 80% of infected individuals. It is unclear why the immune system is frequently unable to mediate a response capable of controlling HCV replication. Dendritic cells (DCs) may be an extrahepatic site of viral replication and it is hypothesised that expression of the core protein within DCs may impair their functions resulting in inadequate immune responses. To investigate potential immunomodulatory effects of the core protein on DCs, replication-deficient adenoviral vectors co-expressing different versions of the core protein (full-length, truncated and a version lacking residues 125-144) with GFP were constructed. Whilst these adenoviruses were being generated, experiments were carried out with an adenoviral vector expressing all the HCV structural proteins (Ad- CE1E2). These experiments revealed no effects of the core protein on DC phenotypic or functional maturation in response to LPS, TNFa or anti-CD40 stimulation. The core protein also had no effect on the ability of DCs to take up antigen and to stimulate allogenic and antigen-specific T cell responses. The core protein has also been proposed to alter the sensitivity of cells to apoptosis; experiments performed in this thesis did not support this, as the susceptibility of DCs to apoptosis induced via the Fas-Fas ligand, TRAIL and lymphotoxin pathways was not affected by core protein expression within these cells. The susceptibility of cells to lysis by natural killer cells and CDS" cytotoxic cells was also not altered by expression of the core protein within them. These results do not support the core protein making a contribution to HCV persistence by immunomodulatory effects on DCs, although it remains possible that core protein expression at higher levels and/or at different intracellular sites within DCs could affect their functions. Acknowledgements I would like to thank my supervisor Dr Persephone Borrow for the opportunity to work in her group and for her eternal optimism, support and encouragement during my PhD. Thank you to all of the members of the viral immunology group, both past and present for their help during my PhD: Julie Lewis, Miranda Ashton, Mai Lee Wong, Valerie Walshe and Eriko Yamada for technical support and friendship. Dr Mike Riffkin and Dr Fabrizio Mattei for help with molecular biology. Dr Lite Meier and Dr Matthew Edwards for helpful discussions and advice, and to Dr Maria Montoya and Dr Simone Gloster for technical help. Thank you to Dr Steven Smith for help making adenoviruses and to Andrew Worth for teaching me confocal microscopy. Thank you to our collaborators. Dr John McLauchlan for providing me with the HCV core protein fragments and antibodies required for this project. Dr Mario Stevenson for providing Ad-GFP and Dr Berwyn Clarke for providing Ad-CE1E2. I am grateful to GlaxoSmithkine for providing GM-CSF and IL-2 and to Dr He and Dr Vogelstein for providing me with the Ad-Easy system for generating recombinant adenoviruses. Thank you to all the volunteers within the Edward Jenner Institute who donated blood for my studies. I would also like to thank my family and friends for supporting me throughout the good and not so good times of my PhD! Table of Contents ABSTRACT 2 ACKNOWLEDGEMENTS 3 TABLE OF CONTENTS 4 LIST OF TABLES & FIGURES 8 ABBREVIATIONS 12 CHAPTER 1 - INTRODUCTION 16 1.1 Introduction 16 1.2 Hepatitis C Virus 17 1.2.1 HCV Classification 17 1.2.2 HCV Genotypes 18 1.2.3 HCV Quasispecies 20 1.3. Virology 21 1.3.1 HCV lifecycle 23 1.3.2 The Structural Proteins 25 1.3.2.1 The core protein 25 1.3.2.2 The Envelope Glycoproteins 29 1.3.3 HCV Cellular Receptors 31 1.3.4 The Non-Structural Proteins 33 1.3.4.1 F Protein 33 1.3.4.2 NS2&P7 33 1.3.4.3 NS3 35 1.3.4.4 NS4 35 1.3.4.5 NS5 36 1.3.5 Models of HCV Replication 37 1.3.5.1 Molecular Clones 38 1.3.5.2 Replicons 39 1.3.6 HCV Tropism 41 1.4 Human Infection & Disease Pathogenesis 42 1.4.1 HCV Transmission 42 1.4.2 Human HCV Infection & Pathogenesis 43 1.4.2.1 Acute HCV . 43 1.4.2.2 Chronic Hepatitis 44 1.4.2.3 Cirrhosis 45 1.4.2.4 Hepatocellular Carcinoma 46 1.4.2.5 Extrahepatic Manifestations 46 1.5 Treatment of HCV Infection & Vaccine Prospects 47 1.5.1 Current Treatment of HCV Infection 47 1.5.2 Prospects for a HCV Vaccine 49 1.6 Models of HCV Disease 55 1.6.1 The Chimpanzee Model 55 1.6.2 Alternative Non-human Primate Approaches 56 1.6.3 Mouse Models 57 1.7 The Immune Response during HCV Infection 59 1.7.1 Overview of the antiviral immune response 59 1.7.2 Innate Immune Responses, and their role in HCV infection 62 1.7.2.1 Type 1 Interferon Response 62 1.7.2.2 Other Innate Cytokines 65 1.7.2.3 Natural Killer & Natural Killer T Cells 66 1.7.2.4 Gamma Delta T Cells 68 1.7.2.5 Complement 68 1.7.3 Adaptive Immune Responses and their role in HCV infection 69 1.7.3.1 Humoral Responses 69 1.7.3.2 CD4* T Cell Responses 72 1.7.3.3 CD8"’ T Cell Responses 74 1.7.4 Immunopathological Role of the Immune Response in HCV-associated Liver Damage 80 1.7.5 Implications for Vaccine Development 82 1.8 Viral Immune Evasion Strategies 83 1.8.1 General Immune Evasion Strategies used by Viruses 83 1.8.1.1 Interference with the induction ormaintenance of host immune responses 84 1.8.1.2 Avoidance of recognition by the host immune response 85 1.8.1.3 Resistance to host effector mechanisms 87 1.8.2 HCV Immune Evasion Strategies 88 1.8.2.1 Type 1 Interferons 89 1.8.2.2 NK Cells 90 1.8.2.3 Antibody Response 91 1.8.2.4 T Cell Responses 92 1.8.3 Potential Involvement of the HCV Core Protein in HCV Evasion Strategies 94 CHAPTER 2 - MATERIALS & METHODS 97 2.1 Materials 97 2.1.1 Biochemical Reagents 97 2.1.2 Plastic ware 100 2.1.3 Restriction Enzymes 101 2.1.4 Plasmids 102 2.1.5 Tissue Culture Reagents 102 2.1.6 Cytokines 103 2.1.7 Antigens & Peptides 104 2.1.8 Cell Lines 104 2.1.9 Kits 104 2.1.10 Antibodies 104 2.2 Methods 107 2.2.1 Preparation & Quantification of Plasmid DNA 107 2.2.2 Preparation & Gel Purification of Plasmid Fragments 108 2.2.3 Subcloning Techniques 109 2.2.4 Plasmid DNA Maxipreps 109 2.2.5 Plasmid Recombination in E.coli BJ5183 Competent Cells 111 2.2.6 Polymerase Chain Reaction (PGR) 111 2.2.7 293 & 293T Cells 112 2.2.8 Generation of Recombinant Adenoviruses 113 2.2.9 CPE Assay 115 2.2.10 Generation of Ad-GFP & Ad-CEI E2 Stocks 116 2.2.11 Adenovirus Purification 117 2.2.12 Peripheral Blood Mononuclear Cell (PBMC) Isolation 118 2.2.13 Human Monocyte-Derived Dendritic Cell (DC) Production 118 2.2.14 Infection of Monocyte-derived Dendritic Cells with Adenoviruses 119 2.2.15 Assessment of GFP Expression by Flow Cytometry 120 2.2.16 Investigation of HCV Core Protein Expression by Confocal Microscopy 120 2.2.17 Stimulation of Monocyte-derived Dendritic Cell Maturation 121 2.2.18 Production of Monocle-derived Macrophages 122 2.2.19 Infection of Monocyte-derived Macrophages with Adenoviruses 122 2.2.20 Analysis of Cell Surface Marker Expression by Flow Cytometry 123 2.2.21 Dextran Uptake by Dendritic Cells 124 2.2.22 Cytokine ELISAs 125 2.2.23 Mixed Lymphocyte Reactions (MLR) 126 2.2.23.1 Proliferation 126 2.2.23.2 IL-2 Production & T Cell Surface Marker expression 127 2.2.24 Stimulation of antigen-specific T cell responses 128 2.2.24.1 IFNy ELISPOT Assay 128 2.2.24.2 Antigen-Specific Proliferation Assays 130 2.2.25 Induction of Apoptosis 131 2.2.26 Natural Killer (NK) Cell Assay 132 2.2.27 Generation of antigen-specific CD8* cytotoxic T cells 134 2.2.28 Culture of Epstein-Barr virus transformed B cell lines 135 2.2.29 CD8^ CTL Cytotoxicity Assays 135 CHAPTER 3 - GENERATION OF RECOMBINANT ADENOVIRUSES EXPRESSING THE HCV CORE PROTEIN 137 3.1 Introduction 137 3.2 Choice of HCV Core Protein and Fragments for Expression in Adenoviral Vectors.
Load more

Recommended publications
  • Old Road Campus
    Old Road Campus 4a, 4b, 4c, U5 n o t Oxford City Centre g OLD ROAD n i d 4a, 4b, 4c, U5 a e H K O L L A D R O W AD E M I L 4,4a,4b,4c, U1X,U5 A41 42 4,4a,4b,4c,U5 Rin D 4 g R oad 6 7 1 13 3 11 C H U R C H I L L 900 D 2 R I 700, 900 V E E O x f o 5 A C rd 12 C i ty 10 C e n t re B 8 CAR PARK C 9 h u r c R F h i O l l O S H E o V s N E p L i T t DRI a VE ENTRANCE ROOSEVELT DRIVE l 900, ST2 Index 1 The Triangle Nursery 9 Old Road Campus Estates Annexe 13 Boundary Brook House Interserve Joint Research Office Kennedy Institute 2 - Research Services, Medical Sciences Division Old Road Campus Research Building 10 - Clinical Trials and Research Governance 3 New Richards Building Department of Oncology - Human Tissue Governance CRUK/MRC Oxford Institute for Radiation Oncology - Medical Sciences Division Business Development 4 NDM Research Building Institute of Biomedical Engineering Nuffield Department of Primary Care Health Sciences Target Discovery Institute Jenner Institute Medical Sciences Divisional Safety Officers Centre for Tropical Medicine and Global Health Bodleian Knowledge Centre (Library Services) Medical Sciences Division IT Services 5 Wellcome Centre for Human Genetics (WHG) Ludwig Institute for Cancer Research Structural Genomics Consortium 6 Henry Wellcome Building for Molecular Physiology Nuffield Department of Surgical Sciences Loading Bays and Delivery Offices of the Nuffield Professor of Medicine ENTRANCE VIA BUILDING 5 11 Big Data Institute A Wellcome Trust Centre for Human Genetics 7 Henry Wellcome Building for Particle Imaging
    [Show full text]
  • Astrazeneca-Oxford Vaccine Approved for Use in the U.K
    P2JW366000-6-A00100-17FFFF5178F ****** THURSDAY,DECEMBER 31,2020~VOL. CCLXXVI NO.154 WSJ.com HHHH $4.00 DJIA 30409.56 À 73.89 0.2% NASDAQ 12870.00 À 0.2% STOXX 600 400.25 g 0.3% 10-YR. TREAS. À 3/32 , yield 0.926% OIL $48.40 À $0.40 GOLD $1,891.00 À $10.50 EURO $1.2300 YEN 103.21 Deadly Attack at Airport Targets New Yemen Government U.S. IPO What’s News Market Reaches Business&Finance Record nvestorspiled into IPOs Iat a record rate in 2020, with companies raising Total $167.2 billion via 454 of- ferings on U.S. exchanges this year through Dec. 24. Few see signs of letup Few expect the euphoria after companies raise to wear off soon. A1 more than $167 billion Detenteisending in the global fight over tech taxes, despite pandemic with Franceresuming collec- tion of itsdigital-services tax BY MAUREEN FARRELL and the U.S. poised to retali- atewith tariffs.Other coun- Defying expectations,inves- tries areset to join the fray. A1 S tors piled intoinitial public of- China finished 2020 PRES feringsatarecordrateiN with a 10th consecutive TED 2020, and few expect the eu- month of expansion in its CIA phoria to wear off soon. manufacturing sector. A7 SO Companies raised $167.2 AS TheEUand China agreed TENSIONS HIGH: People fled after an explosion Wednesday at the airport in Aden, Yemen, moments after members of the billion through 454 offerings in principle on an invest- country’s newly sworn-in cabinet arrived. At least 22 people were killed, but all the members of the cabinet were safe.
    [Show full text]
  • Annual Meeting
    Volume 97 | Number 5 Volume VOLUME 97 NOVEMBER 2017 NUMBER 5 SUPPLEMENT SIXTY-SIXTH ANNUAL MEETING November 5–9, 2017 The Baltimore Convention Center | Baltimore, Maryland USA The American Journal of Tropical Medicine and Hygiene The American Journal of Tropical astmh.org ajtmh.org #TropMed17 Supplement to The American Journal of Tropical Medicine and Hygiene ASTMH FP Cover 17.indd 1-3 10/11/17 1:48 PM Welcome to TropMed17, our yearly assembly for stimulating research, clinical advances, special lectures, guests and bonus events. Our keynote speaker this year is Dr. Paul Farmer, Co-founder and Chief Strategist of Partners In Health (PIH). In addition, Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases, will deliver a plenary session Thursday, November 9. Other highlighted speakers include Dr. Scott O’Neill, who will deliver the Fred L. Soper Lecture; Dr. Claudio F. Lanata, the Vincenzo Marcolongo Memorial Lecture; and Dr. Jane Cardosa, the Commemorative Fund Lecture. We are pleased to announce that this year’s offerings extend beyond communicating top-rated science to direct service to the global community and a number of novel events: • Get a Shot. Give a Shot.® Through Walgreens’ Get a Shot. Give a Shot.® campaign, you can not only receive your free flu shot, but also provide a lifesaving vaccine to a child in need via the UN Foundation’s Shot@Life campaign. • Under the Net. Walk in the shoes of a young girl living in a refugee camp through the virtual reality experience presented by UN Foundation’s Nothing But Nets campaign.
    [Show full text]
  • Jenner Institute Complementary Vaccines Platform Technologies
    WHO R&D Blueprint: Janssen Vaccines – Jenner Institute complementary Vaccines Platform Technologies Janssen Vaccines: Jenner Institute: Olga Popova Prof. Sarah Gilbert Jerome Custers WHO Geneva, 21 July 2016 Background • Jenner Institute & Janssen Vaccines presented respective proposals to WHO R&D Blueprint Workshop in April 2016, and were invited to join forces for Round 2 submission • Example of alignment, coordination and partnership between public and private sector stakeholders • Understanding nature of vaccine development, established complementary end‐to‐end skills and capabilities • Long‐term, sustainable & consistent approach and funding • High‐level flexible proposal with illustrative examples • «Bona fide»: collaborative framework to be developed JOINTLY TOWARDS TANGIBLE OUTCOMES x GLOBAL PUBLIC HEALTH 2 Success factors • Available platforms and previous experience with pathogens • Ability to invest time and resources, leverage expertise, minimise opportunity costs and ensure business continuity • Appropriate and functionable operational model, speed • Lean governance, partner alignment and milestone orientation INTERNAL • Reliable & qualified partners, durable commitments • Long‐term reliable funding (min 5‐year horizon) • Resolving vaccination indemnification / liability issue • Consistency in pathogen prioritisation and defined, consistent pre‐ established endpoint commitment • Clear and accelerated / streamlined regulatory pathways, conditions & predictability of licensure EXTERNAL • Anticipated deployment plans and community
    [Show full text]
  • Sir Bryn Terfel Premieres John Rutter's 'Joseph's Carol', Dedicated to the Oxford Vaccine Team in Celebratory Concert Fr
    Sir Bryn Terfel premieres John Rutter’s ‘Joseph’s Carol’, dedicated to the Oxford vaccine team in celebratory concert from the Oxford Philharmonic Orchestra Friday 18 December 2020, 18:30 Streamed on Oxford Philharmonic Orchestra’s YouTube Channel: bit.ly/OPOVaccineTribute Elgar Chanson de Matin William Henry Monk Abide with Me Rodgers & Hammerstein You’ll Never Walk Alone John Rutter Joseph’s Carol WORLD PREMIERE John Rutter Look to the Day Handel Hallelujah Chorus Sir Bryn Terfel bass-baritone Oxford Philharmonic Orchestra Maxim Vengerov violin Choir of Merton College, Oxford John Rutter conductor Alexandra Lowe soprano Marios Papadopoulos conductor Alexander Olleson treble John Suchet presenter In recognition of the formidable work accomplished by the team of scientists at the University of Oxford on their Covid-19 vaccine, the Oxford Philharmonic Orchestra will stream a celebratory concert on Friday 18 December, recorded in the city’s historic Sheldonian Theatre. Performed by bass-baritone Sir Bryn Terfel, the short concert features the premiere of John Rutter’s Joseph’s Carol, written in tribute to the Oxford Vaccine Group, the Jenner Institute and the RECOVERY team. The words by John Rutter recount the long and weary journey of Joseph and Mary to Bethlehem before the birth of the baby Jesus, echoing the programme’s journey from struggle through to hope. Bryn Terfel also joins the Orchestra and the Choir of Merton College, Oxford, in a rousing programme from Rodgers & Hammerstein’s You’ll Never Walk Alone (with Jette Parker Young Artist Alexandra Lowe) to Handel’s Hallelujah Chorus. Sir Bryn and the Orchestra are also joined in the hymn of comfort, Abide with Me, by chorister Alexander Olleson of Christ Church Cathedral Choir, the recent winner of BBC Young Chorister Of The Year 2020.
    [Show full text]
  • 'Astrazeneca' Covid-19 Vaccine
    Medicines Law & Policy How the ‘Oxford’ Covid-19 vaccine became the ‘AstraZeneca’ Covid-19 vaccine By Christopher Garrison 1. Introduction. The ‘Oxford / AstraZeneca’ vaccine is one of the world’s leading hopes in the race to end the Covid-19 pandemic. Its history is not as clear, though, as it may first seem. The media reporting about the vaccine tends to focus either on the very small (non-profit, academic) Jenner Institute at Oxford University, where the vaccine was first invented, or the very large (‘Big Pharma’ firm) AstraZeneca, which is now responsible for organising its (non-profit) world-wide development, manufacture and distribution. However, examining the intellectual property (IP) path of the vaccine from invention to manufacture and distribution reveals a more complex picture that involves other important actors (with for-profit perspectives). Mindful of the very large sums of public money being used to support Covid-19 vaccine development, section 2 of this note will therefore contextualise the respective roles of the Jenner Institute, AstraZeneca and these other actors, so that their share of risk and (potential) reward in the project can be better understood. Section 3 provides comments as well as raising some important questions about what might yet be done better and what lessons can be learned for the future. 2. History of the ‘Oxford / AstraZeneca’ vaccine. 2.1 Oxford University and Oxford University Innovation Ltd. The Bayh-Dole Act (1980) was hugely influential in the United States and elsewhere in encouraging universities to commercially exploit the IP they were generating by setting up ‘technology transfer’ offices.
    [Show full text]
  • Job Description and Person Specificationselection Criteria
    Job title Senior Postdoctoral Scientist Division Medical Sciences Department Nuffield Department of Medicine, Jenner Institute Clinical Centre for Vaccinology and Translational Medicine Location (CCVTM), Old Road Campus, Headington, Oxford, OX3 7LE Grade 8: £41,526 - £49,553 per annum with a discretionary range Grade and salary to £54,131 per annum Hours Full time Contract type Fixed-term contract for 20 months, in the first instance Reporting to Professor Christine Rollier & Professor Cal MacLennan Vacancy reference 147960 Additional Position funded by US funding information Development of a Gonococcal Outer Membrane Vesicle Vaccine Research topic from Lead Optimization to Phase 1 Clinical Trial Principal Investigator Professor Christine Rollier & Professor Cal MacLennan / supervisor Project team Gonococcal Vaccine Group http://www.jenner.ac.uk/ Project web site Funding partner US funding 1. Gottlieb SL, et al. Gonococcal vaccines: public health value and preferred product characteristics; report of a WHO global stakeholder consultation, January 2019. Vaccine 2020; 38: 4362-4373. 2. Micoli, F et al. Comparative immunogenicity and efficacy of equivalent outer membrane vesicle and glycoconjugate vaccines against nontyphoidal Salmonella. PNAS 2018; Recent publications 115: 10428-33. 3. Folegatti PM, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet 2020; 396: 467-478. 4. Marsay L, et al. A novel meningococcal outer membrane vesicle vaccine with constitutive expression of FetA: A phase I clinical trial. J Infect 2015; 71: 326-37. The Role The Gonococcal Vaccine Project is based at the Jenner Institute, University of Oxford, and utilizes a novel outer membrane vesicle (OMV) technology to develop a vaccine against gonorrhoea.
    [Show full text]
  • ASTMH 65Th Annual Meeting Atlanta Marriott Marquis and Hilton Atlanta Atlanta, GA Pre-Registration List As of October 27, 2016
    ASTMH 65th Annual Meeting Atlanta Marriott Marquis and Hilton Atlanta Atlanta, GA Pre-Registration List as of October 27, 2016 *John Aaskov, PhD FRCPath Denise Abud Oladokun Adedamola Adesunloye, Queensland University of Technology Sanofi Pastuer Federal Ministry of Health(FMC) Australia USA Nigeria Neetu Abad Manfred M K Accrombessi Grace Adeya CDC Benin GHSC-PSM/Chemonics United States USA *Jane Winnie Achan, Clinical *Tochukwu Abadom MRC Unit, The Gambia Bwaka Mpia Ado Blackpool Victoria Hospital, United Gambia McKIng Consulting Corporation/ EPI Kingdom DRC Nigeria *Nicole L. Achee, PhD Dem. Republic of Congo Univ of Notre Dame *Shaymaa Abdalal, MD USA Joseph Ado-Yobo Tulane School of Public Hlth Ghana USA Salissou Adamou Bathiri Onchocerciasis & Lymphatic *Valentine Adolphe *Agatha Aboe, MBChB; DO Niger PSI Sightsavers USA Ghana *David P. Adams, PhD MPH MSc Dept of Community Medicine, Mercer Yaw Asare Afrane *Ayokunle Abogan Univ Sch of Medicine Kenya Medical Research Institute Natl Malaria Programme USA Kenya Botswana *John H. Adams, PhD Suneth Agampodi, MBBS MSc *Melanie Abongwa, MSc University of South Florida Coll of Pub Univ of Sri Lanka Iowa State University Hlth Sri Lanka USA USA *Kokila Agarwal, DRPH MBBS MPH *Ahmed Abd El Wahed Abou El Nasr, *Matthew Adams MCHIP/JHPIEGO Georg August University Goettingen Univ of Maryland Baltimore USA Germany USA Kodjovi D. Agbodjavou *Jennifer Abrahams, MD Marc Adamy Jhpiego Corp University of Miami/Jackson Memorial Medicines for Malaria Venture Togo Hospital Switzerland USA Rakesh Aggarwal, MD DM *David Addiss, MD MPH Sanjay Gandhi Postgraduate Inst of Lauren Abrams, GA Task Force for Global Hlth Med Sciences Children Without Worms USA India United States *Ahmed Adeel, MD MPH PhD *Selidji Todagbe AGNANDJI Marcelo Claudio Abril United States CERMEL Fundación Mundo Sano Gabon Argentina *Adeshina Israel Adekunle UNSW *Peter C.
    [Show full text]
  • University of Oxford Oxford OX3 7LE
    Prof Adrian Hill Centre for Clinical Vaccinology & Chief Investigator Tropical Medicine (CCVTM) The Jenner Institute Churchill Hospital University of Oxford Oxford OX3 7LE Recruitment Co-ordinator National Research Ethics Service Tel: 01865 611424 Committee: South Central Oxford A Fax: 01865 289694 Number: 17/SC/0552 Email: [email protected] PARTICIPANT INFORMATION SHEET: MERS001 A study to assess the new candidate MERS-CoV vaccine in healthy adults “A phase I study to determine the safety and immunogenicity of the candidate Middle East Respiratory Syndrome Coronavirus (MERS-CoV) vaccine ChAdOx1 MERS in UK healthy adult volunteers” We would like to invite you to take part in a research study. Before you make a decision, it is important you take the time to understand why the research is being done and what it would involve. Please read the following information carefully and discuss it with friends, relatives and your General Practitioner (GP) if you wish. • Part 1 tells you the purpose of the study and what will happen to you if you take part. • Part 2 tells you more information about the conduct of the study. Please ask us if there is anything that is not clear, or if you would like more information. Take time to decide whether or not to take part. PART 1 What is the purpose of this trial? The purpose of this study is to test a new vaccine against the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in healthy volunteers. MERS-CoV has been identified as one of the most worrying newly emerging outbreak diseases by many global agencies and expert groups, including the World Health Organization (WHO).
    [Show full text]
  • MALARIA VACCINES for the WORLD 2-4 May 2016, Leiden University Medical Center LUMC, Leiden, the Netherlands
    THE FOURTH INTERNATIONAL CONFERENCE ON: MALARIA VACCINES FOR THE WORLD 2-4 May 2016, Leiden University Medical Center LUMC, Leiden, The Netherlands SECOND CIRCULAR AND PROVISIONAL CONFERENCE PROGRAMME FOR MVW 2016 With more an estimated 200 million clinical cases annually, resulting in more than 580,000 deaths, malaria is not only an important global health problem but also a major factor limiting economic development in developing countries. Interventions that deploy an effective malaria vaccine are regarded as being one of the most cost-effective and reliable means to limit and ultimately eradicate the disease. In recent years, due to increased funding and research, malaria vaccine development has greatly accelerated. The MVW 2016 conference will look at different aspects of vaccine development, assessment and deployment, as well as funding and regulatory aspects of vaccine implementation and testing. The conference will also highlight research on the use of animal models and (controlled) clinical trials to study the immunological basis of protection and to identify novel candidate vaccine antigens. The MVW 2016 meeting will be of interest to scientists, physicians and other professionals from the academic, industrial/commercial and governmental/policy/regulatory sectors that have an interest in vaccine development and global health. The meeting will include talks on: Malaria vaccine candidate discovery · Novel pre-clinical screening assays/models · Vaccine immunology including system-based approaches · Correlates of protection after vaccination · Pre-erythrocytic vaccines and vaccination · Vaccines for interrupting malaria transmission: role in elimination strategies · RTS,S implementation and refinements · Vaccines against blood stage of malaria infection and multi-stage vaccines · Clinical trials of malaria vaccines controlled human malaria infections (CHMI) and field trials · Relevance and issues related to first in man trials and CHMI studies in endemic countries · Modelling and measuring long-term malaria vaccine impact.
    [Show full text]
  • Isis Insights 63
    The research commercialisation office of the University of Oxford, previously called Isis Innovation, has been renamed Oxford University Innovation All documents and other materials will be updated accordingly. In the meantime the remaining content of this Isis Innovation document is still valid. URLs beginning www.isis-innovation.com/... are automatically redirected to our new domain, www.innovation.ox.ac.uk/... Phone numbers and email addresses for individual members of staff are unchanged Email : [email protected] Ii 63 Spring 11 Issue Isis insights The latest innovations, collaborations and technology transfer Healthy futures Screening for discovery... IiContents Issue 63 Healthy futures Screening for discovery... Tackling Tuberculosis 10 Protein Superglue 26 Patient Reported Outcomes 28 03. Newsflash 18. Transformers The latest news from Isis Lightweight motor magnets 04. The Loop 20. Testing, Testing A news roundup from Oxford University Making test tube research more reliable Consulting and Isis Enterprise 22. Spring Clean 05. The Portfolio Showcasing clean-tech energy systems Investment and spin-out news 24. Fluid Thinking 06. Technology Steps Forward An acoustic separator for a wide audience The latest licence agreements 26. Protein Superglue Identifying proteins linked with diseases 08. Scouting for Success Oxford Innovation Society member Dow Chemical’s investment strategies 28. The PROs of Academic Consultancy Oxford University Consulting helping with 10. Tackling Tuberculosis healthcare A vaccine for the 21st Century 30. Above Sea Level 12. Oxford-Emergent Tuberculosis Isis Enterprise using submarine technology for Consortium Focus health screening Deeper insight into the TB vaccine partnership 16. Inside the Incubator A new initiative for Oxford software Ii is produced by Isis Innovation Ltd, the technology transfer company owned by the University of Oxford.
    [Show full text]
  • Vice-Chancellor's Oration 2016
    WEDNESDAY 12 OCTOBER 2016 • SUPPLEMENT (1) TO NO 5144 • VOL 147 Gazette Supplement Vice-Chancellor’s Oration 2016 One Oxford four divisions, Humanities, Social Sciences, the Humanities. I have read the books sent MPLS and Medicine, whose research is me by academics like Diego Gambetta's Good morning. Colleagues and friends of responsible for this ranking. Engineers of Jihad and Senia Paseta's Irish Nationalist Women. I have met with the University, thank you for taking time My first nine months have been an remarkable young people such as our Moritz to attend the ceremony this morning, and extraordinary and exhilarating experience Heyman scholars, students participating to listen to my perspective and reflections as I have sought to learn as much as I can in the UNIQ summer school, on the LMH as I begin my first academic year as Vice- about the life and work of the University. Foundation year and in the IntoUniversity Chancellor. I have attended strategy meetings of programs, and so many others. I have also divisions, departments and colleges. I have Before we begin, I think we should sit back, on occasion tried to relax in our wonderful spoken to students in their colleges, clubs, take a deep breath, and contemplate the museums, gardens and parks. Not a day goes societies, in open office hours and over fact that we have just been named the by but I reflect on just how fortunate I am to tea. I have attended lectures on Race in the best university in the world, by the most be a part of this place.
    [Show full text]