Professor David Cameron Wraith

Image of David Wraith

Institute of Immunology and Immunotherapy
Professor of Immunology
Director of the Institute of Immunology and Immunotherapy

Contact details

Address
Institute of Immunology and Immunotherapy
College of Medical and Dental Sciences
Institute of Biomedical Research
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

David Wraith is an immunologist who has worked in the field of T cell biology for over 35 years. He is best known for his ground-breaking work on autoimmunity and immunotherapy. His research team has revealed mechanisms whereby autoreactive T-cells escape deletion in the thymus and thus appear in the repertoire of all individuals. He also demonstrated that autoreactive T-cells can be silenced by suitable administration of fragments of their protein targets. This highly focused immunotherapy involves a negative feedback mechanism and can be adapted for treatment of any autoimmune or allergic disease. His research group has defined the rules governing the design of therapeutic peptides and revealed the molecular basis of the T cell desensitisation that results from their use. He is now developing this form of antigen-specific immunotherapy through Apitope, a company that designs and tests novel treatments for autoimmune conditions in the clinic. Apitope has successfully completed phase 2 clinical trials of peptide immunotherapy in multiple sclerosis and is involved in further trials of the approach in Graves’ disease and haemophilia.

Qualifications

  • PhD in Biochemistry 1981
  • FRSB

Biography

David Wraith began his career in immunology at NIMR, London, working with Professor Brigitte Askonas to define the mechanism by which immune cells kill virus infected cells. The aim of this work was to devise a vaccine that would provide better protection against the influenza virus. With Townsend, McMichael and colleagues he demonstrated that cytotoxic T cells respond to peptide fragments of antigen. David developed a vaccine based on the influenza viral nucleoprotein and showed that this would confer immunity against heterotypic infection. 

In 1986 David joined Professor Hugh McDevitt in Stanford where he focused on the immunology of autoimmune diseases. He published influential papers describing how monoclonal antibodies and synthetic peptides could be developed for immunotherapy of autoimmune diseases.

David established his laboratory in Cambridge in 1989 where he continued his research into immunological tolerance and immunotherapy as a Senior Fellow of the Wellcome Trust. In 1995, he was offered the Chair in Experimental Pathology at Bristol and in 1996 was appointed Head of the Department of Pathology and Microbiology. Over the following 5 years, David rebuilt the department, employed new staff and research fellows and in the 2001 RAE, 41 staff members were returned, scoring 5A.

David has sat on grants panels for the MRC, Wellcome Trust, NKRF, ARC, MS Society and the NIH (USA). In 2002, he founded Apitope Ltd as a vehicle for clinical development of peptide therapy in autoimmune diseases and allergies. The company successfully completed clinical trials of its peptide treatment for MS in 2009, 2013 and 2016. Apitope is now developing treatments for autoimmune complications of haemophilia A and for Graves’ disease and Uveitis. The Apitope approach has the potential to treat many serious autoimmune and allergic diseases for which there is currently no effective treatment.

Postgraduate supervision

Professor Wraith has supervised the following PhD students to completion of their PhD. The current position of each student is noted in brackets:

  • Barbara Metzler - Hoffman-La Roche Student [group leader Novartis]
  • Richard Smith - Multiple Sclerosis Society Clinical Fellow [CSL, Cardiff]
  • George Liu - Howard Hughes Predoctoral Fellow [Associate Professor UCLA & PI Cedars Sinai Medical Center]
  • Mary Maceachern - Wellcome Trust Prize Student [Price Waterhouse Cooper]
  • Mark Harber - Wellcome Trust Advanced Clinical Training Fellow/NKRF Training Fellow [Consultant Nephrologist at Royal Free Hospital]
  • Stephan Kissler - MRC/Case Studentship [Associate Professor of Medicine, Harvard Clinical and Translational Science Center and Joslin Diabetes Center, Boston]
  • Emma Massey/O’Neill - Wellcome Trust Prize Student [RCVS Specialist in Internal Medicine and Lecturer UC Dublin School of Veterinary Medicine]
  • Nat Whitley - Wellcome Trust Prize Student [Director and Head of Medicine, Davies Veterinary Specialists, London]
  • Kirsty Nicolson - Apitope Technology Student [Group Leader, Huntingdon Life Sciences]
  • Leona Robinson - MS Society Student [MRC Staff, CRICK institute]
  • Rachel Protheroe - Wellcome Trust Clinical Training Fellow [Consultant Haematologist, BRI, Bristol]
  • Bronwen Burton - Institute of Child Health Studentship [Research Fellow, University of Bristol]
  • Masriana Hassan - Fellowship of the University Putra, Malaysia [Lecturer, University of Putra, Malaysia]
  • Graham Britton - Wellcome Trust Programme in Dynamic Cell Biology [Research Fellow, Icahn School of Medicine at Mount Sinai, New York]
  • Shang Zhang - [Staff Scientist, Grandhope Biotech Ltd, China]
  • Laura Carney - Wellcome Trust Programme in Dynamic Cell Biology [Marks and Clerk LLP, Patent Attorneys]
  • Ruth Mitchell - Wellcome Trust Programme in Dynamic Cell Biology [Elizabeth Blackwell Institute, Research Fellow, University of Bristol]
  • Helen Tunbridge - Wellcome Trust Programme in Dynamic Cell Biology [Adaptimmune Ltd]
  • Sky Ng - [Immune Tolerance Network Postdoctoral Research Fellow, University of Bristol]

If you are interested in studying with Professor Wraith please contact him directly on the contact details above, or for any general doctoral research enquiries, please email: dr@contacts.bham.ac.uk or call +44 (0)121 414 5005.

For a full list of available Doctoral Research opportunities, please visit our Doctoral Research programme listings.

Research

David Wraith has worked in the field of T cell biology and the role of T lymphocytes in protection from infection and in autoimmunity since 1981. 

Since 1995 his laboratory in Bristol has focused on the mechanism of antigen-specific immunotherapy. His work provided the essential rules governing the design of therapeutic peptides and led to the establishment of a University of Bristol spinout company, Apitope NV (www.apitope.com). The company has designed peptides for treatment of various autoimmune diseases and has successfully completed phase 2 trials in relapsing multiple sclerosis. David’s research laboratory is currently defining the differentiation pathway of antigen induced Treg cells and the mechanism by which these cells suppress disease. The aim of this approach is to improve the efficacy of peptide therapy for treating allergic and autoimmune diseases in man.

In 1986 and 1987 David was awarded MRC and National MS Society fellowships to work in the laboratory of Hugh McDevitt in Stanford. Their work described how monoclonal antibodies and synthetic peptides could be developed for immunotherapy of autoimmune diseases. In 1989, David was awarded the Wellcome Trust Senior Fellowship to establish a new laboratory in Cambridge working on mechanisms of immunological tolerance; his group was among the first to demonstrate induction of peripheral tolerance by administration of soluble peptide antigens. 

David originally trained as an immunologist with Ita Askonas at the National Institute for Medical Research, Mill Hill where he worked on the mechanism whereby cytotoxic T cells respond to and kill influenza virus infected cells through recognition of peptide fragments of antigen. His work also led to the development of a vaccine that induced cytotoxic T cells capable of heterotypic immunity.

Other activities

Academic Research Responsibilities

  • Former member of Wellcome Trust Infection and Immunity Panel; Wellcome Trust Expert Review Group ‘Immune System in Health and Disease’; MRC Infections and Immunology Board and research grant panels for Arthritis Research UK, MS Society UK, National Kidney Research Fund and National Institutes of Health, USA
  • MRC Prion Unit (Scientific Advisory Group)
  • Manchester Collaborative Centre for Inflammation Research (Scientific Advisory Board)

Industry Responsibilities

  • Founder of and CSO for Apitope Technology (Bristol) Ltd & Apitope International NV
  • Past member of Scientific Advisory Boards for Peptide Therapeutics Ltd (UK), TEVA (Israel) and GSK BIO (Belgium)
  • Advisor to Hoffman La Roche on autoimmune therapeutics; DTI on Stem Cell Therapies; Food Standards Agency on Peanut Allergy; Novartis on Influenza Vaccine Safety; Actelion Pharma, Technology Strategy; Zealand Pharma, Technology Strategy
  • Expert witness at the European Patent Office, Opposition Division and Technical Boards of Appeal

Publications

White, A.M. and Wraith, D.C. Tr1-Like T Cells – An Enigmatic Regulatory T Cell Lineage. Front. Immunol. (2016) 7:355. doi: 10.3389/fimmu.2016.00355

Selli, M., Wick, G., Wraith, D. and Newby, A. Autoimmunity to HSP60 during diet induced obesity in mice. Int. J. Obesity (2016) 348: 348-351

Britton, G.J., Ambler, R., Clark, D.J., Hill, E.V., Tunbridge, H.M., McNally, K.E., Burton, B.R., Butterweck, P., Sabatos-Peyton, C., Hampton-O’Neil, L.A., Verkade, P., Wuelfing, C. and Wraith, D.C. PKCq links proximal T cell and Notch signaling through localized regulation of the actin cytoskeleton. eLIFE (2017) 10.7554/eLife.20003

Wegner, A., Verhagen, J. and Wraith, D.C. Myeloid-derived suppressor cells mediate tolerance induction in autoimmune disease. Immunology (2017) 151: 26-42

Britton, G.J., Mitchell, R.E., Burton, B.R. and Wraith, D.C. Protein Kinase C theta is required for efficient induction of IL-10-secreting T cells. PLoS ONE (2017) 12, 2, e0171547

Selli, M.E., Thomas, A.C., Wraith, D.C. and Newby, A.C. A humanized HLA-DR4 mouse model of autoimmune myocarditis. Journal of Molecular and Cellular Cardiology 107 (2017) 22–26

Mitchell, R.E., Hassan, M., Burton, B.R., Britton, G., Hill, E.V., Verhagen, J. and Wraith, D.C. IL-4 enhances IL-10 production in Th1 cells: implications for Th1 and Th2 regulation. Scientific Reports (2017) 7:11315

Kishore, M., Cheung, K.C.P., Fu, H., Bonacina, F., Wang, G., Coe, D., Ward, E.J., Colamatteo, A., Jangani, M., Baragetti, A., Matarese, G., Smith, D.M., Haas, R., Mauro, C., Wraith, D.C., Okkenhaug, K., Catapano, A.L., De Rosa, V., Norata, G.D., and Marelli-Berg, F.M. Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis. Immunity (2017) 47: 875-889

Wraith, D.C. The future of immunotherapy: a 20-year perspective. Front. Immunol. (2017) 8:1688

Wraith, D.C. Designing antigens for the prevention and treatment of autoimmune diseases. Current Opinion in Chemical Engineering (2018) 19: 35-42

Chataway, J., Martin, K., Barrell, K., Sharrack, B., Stolt, P. & Wraith, D.C. Effects of ATX-MS-1467 immunotherapy over 16 weeks in relapsing multiple sclerosis. Neurology (2018) 90, e955-e962

Burton, B.R., Tennant, R.K., Love, J., Titball, R.W., Wraith, D.C., & White, H.N. Variant proteins stimulate more IgM+ GC B-cells revealing a mechanism of cross-reactive recognition by antibody memory. eLife (2018) 7:e26832

Jansson, L., Vrolix, K., Jahraus, A., Martin, K.F. & Wraith, D.C. Immunotherapy with apitopes blocks the immune response to thyroid stimulating hormone receptor in HLA-DR transgenic mice. Endocrinology (2018) 159, 3446-3457

Expertise

Immunology