A human vaccine strategy based on chimpanzee adenoviral and MVA vectors that primes, boosts, and sustains functional HCV-specific T cell memory.
Leo Swadling,Stefania Capone,Richard D Antrobus,Anthony Brown,Rachel Richardson,Evan W. Newell,Evan W. Newell,John Halliday,John Halliday,Christabel Kelly,Christabel Kelly,Dan Hameiri Bowen,Joannah R. Fergusson,Ayako Kurioka,Virginia Ammendola,Mariarosaria Del Sorbo,Fabiana Grazioli,Maria Luisa Esposito,Loredana Siani,Cinzia Traboni,Adrian V. S. Hill,Stefano Colloca,Mark M. Davis,Alfredo Nicosia,Riccardo Cortese,Antonella Folgori,Paul Klenerman,Paul Klenerman,Eleanor Barnes,Eleanor Barnes +29 more
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TLDR
A first-in-human trial of a prime-boost vaccine strategy for HCV, with durable, broad, sustained, and balanced T cell responses, characteristic of those associated with viral control, paving the way for the first efficacy studies of a prophylactic HCV vaccine.Abstract:
A protective vaccine against hepatitis C virus (HCV) remains an unmet clinical need. HCV infects millions of people worldwide and is a leading cause of liver cirrhosis and hepatocellular cancer. Animal challenge experiments, immunogenetics studies, and assessment of host immunity during acute infection highlight the critical role that effective T cell immunity plays in viral control. In this first-in-man study, we have induced antiviral immunity with functional characteristics analogous to those associated with viral control in natural infection, and improved upon a vaccine based on adenoviral vectors alone. We assessed a heterologous prime-boost vaccination strategy based on a replicative defective simian adenoviral vector (ChAd3) and modified vaccinia Ankara (MVA) vector encoding the NS3, NS4, NS5A, and NS5B proteins of HCV genotype 1b. Analysis used single-cell mass cytometry and human leukocyte antigen class I peptide tetramer technology in healthy human volunteers. We show that HCV-specific T cells induced by ChAd3 are optimally boosted with MVA, and generate very high levels of both CD8 + and CD4 + HCV-specific T cells targeting multiple HCV antigens. Sustained memory and effector T cell populations are generated, and T cell memory evolved over time with improvement of quality (proliferation and polyfunctionality) after heterologous MVA boost. We have developed an HCV vaccine strategy, with durable, broad, sustained, and balanced T cell responses, characteristic of those associated with viral control, paving the way for the first efficacy studies of a prophylactic HCV vaccine.read more
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Burden of liver disease in Europe: Epidemiology and analysis of risk factors to identify prevention policies
Laura Pimpin,Helena Cortez-Pinto,Francesco Negro,Emily Corbould,Jeffrey V. Lazarus,Laura Webber,Nick Sheron +6 more
TL;DR: Prevalence and mortality data indicate that increasing cirrhosis and liver cancer may be linked to dramatic increases in harmful alcohol consumption in Northern European countries, and viral hepatitis epidemics in Eastern and Southern European countries.
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HLA variation and disease
TL;DR: The scope for personalized antigen-specific disease prevention is evaluated, whereby harnessing HLA–ligand interactions for clinical benefit is becoming a realistic prospect.
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A Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA
Katie J. Ewer,Tommy Rampling,N Venkatraman,Georgina Bowyer,Daniel B. Wright,Teresa Lambe,Egeruan B. Imoukhuede,Ruth O. Payne,Sarah Katharina Fehling,Thomas Strecker,Nadine Biedenkopf,Verena Krähling,Claire M. Tully,Nick J. Edwards,Emma M. Bentley,Dhanraj Samuel,Geneviève M. Labbé,Jing Jin,Malick M. Gibani,Alice Minhinnick,Morven Wilkie,Ian D. Poulton,Natalie Lella,Rachel Roberts,Felicity Hartnell,Carly M. Bliss,Kailan Sierra-Davidson,Jonathan Powlson,Eleanor Berrie,Richard S. Tedder,François Roman,Iris De Ryck,Alfredo Nicosia,Nancy J. Sullivan,Daphne A. Stanley,Olivier Tshiani Mbaya,Julie E. Ledgerwood,Richard M. Schwartz,Loredana Siani,Stefano Colloca,Antonella Folgori,Stefania Di Marco,Riccardo Cortese,Edward Wright,Stephan Becker,Barney S. Graham,Richard A. Koup,Myron M. Levine,Ariane Volkmann,Paul Chaplin,Andrew J. Pollard,Simon J. Draper,W. Ripley Ballou,Alison M. Lawrie,Sarah C. Gilbert,Adrian V. S. Hill +55 more
TL;DR: The chimpanzee adenovirus 3 (ChAd3) vaccine boosted with MVA elicited B-cell and T-cell immune responses to ZEBOV that were superior to those induced by the ChAd3 vaccine alone.
Journal ArticleDOI
Immune responses and immunopathology in acute and chronic viral hepatitis
TL;DR: The similarities and differences in immune responses to and immunopathogenesis of HAV, HBV and HCV infections are discussed, which may explain the distinct courses and outcomes of each hepatitis virus infection.
Journal ArticleDOI
Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine.
R P Payne,S Longet,J A Austin,Donal T. Skelly,Wanwisa Dejnirattisai,Adele S,N Meardon,S Faustini,S Al-Taei,S C Moore,T Tipton,L M Hering,A Angyal,Rebecca Brown,A R Nicols,N Gillson,S L Dobson,A Amini,P Supasa,A Cross,Alice Bridges-Webb,L S Reyes,A Linder,G Sandhar,J A Kilby,J K Tyerman,T Altmann,H Hornsby,R Whitham,E Phillips,T Malone,Andy Hargreaves,Adrian M Shields,A Saei,S Foulkes,L Stafford,Steven Johnson,Daniel G. Wootton,C P Conlon,K Jeffery,P C Matthews,J Frater,A S Deeks,Andrew J. Pollard,A Brown,Sarah Rowland-Jones,Juthathip Mongkolsapaya,Eleanor Barnes,S Hopkins,V J Hall,V J Hall,Christina Dold,Duncan Cja.,A Richter,A Richter,Michael C. Carroll,Gavin R. Screaton,T I de Silva,Lance Turtle,Paul Klenerman,Susanna Dunachie +60 more
TL;DR: In this paper, an extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose, which showed that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T-cell response to the spike protein.
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