Prof Adrian Hill
	Tel:	+44 (0)1865 617 610
	E-mail:	adrian.hill@ndm.ox.ac.uk
	Address:	The Jenner Institute, Old Road Campus Research Building Roosevelt Drive, Oxford OX3 7DQ
	Website:	www.jenner.ac.uk

Principal areas of research
Malaria vaccines, vectored vaccine development, immunogenetics of infectious disease susceptibility

Biography
Adrian Hill trained in medicine at Trinity College Dublin and the University of Oxford, qualifying in 1982.  He undertook a DPhil with Sir David Weatherall and John Clegg at the MRC Molecular Haematology unit on the molecular population genetics of thalassaemia in Pacific Islanders.  Following further clinical posts in London he returned to the newly opened Institute of Molecular Medicine in 1988 to study genetic susceptibility to malaria as a Wellcome Trust Senior Fellow.  In 1995 he was awarded a Wellcome Trust Principal Research Fellowship and in 1996 the title of Professor of Human Genetics.  He participated in the founding of the Wellcome Trust Centre for Human Genetics in 1994, and in 2003 co-founded the Oxford Centre for Clinical Vaccinology and Tropical Medicine, which he now chairs.  In 2004 he participated in the restructuring of the Edward Jenner Institute for Vaccine Research and in 2005 was appointed director of the new Jenner Institute.  He is a Fellow of the Royal College of Physicians, of Magdalen College, Oxford, and of the UK Academy of Medical Sciences.

Research
Dr Hill’s detailed analyses of HLA polymorphism and malaria susceptibility in African children led to an interest in vaccine development, particularly assessing T cell-inducing vaccines against malaria. In murine studies he identified the enhanced T cell immunogenicity of non-replicating poxviruses as boosting agents in vaccination protocols.  This led to phase I clinical trials of both DNA and MVA vaccines for malaria starting in 1999.  His group showed the first T cell mediated protection of human vaccinees by using DNA-MVA and fowlpox-MVA prime-boost regimes against malaria. 

To achieve greater levels of protective efficacy his group is currently developing more immunogenic prime-boost regimes involving recombinant adenoviruses are priming agents and MVA as a boosting agent.  This regime has shown excellent immunogenicity in pre-clinical studies in mice and macaques.  More immunogenic vectored vaccines are being developed as part of a major grant from the Foundation for NIH and the Gates Foundation addressing one of the Grand Challenge in Global Health.  In this work several internal adjuvants have been identified that enhance the immunogenicity of vectored vaccines.
To avoid the problem of anti-vector immunity associated with use of common human serotypes of adenovirus as vaccine vectors, extensive studies of simian adenoviruses have been undertaken.  This has led to the identification of a lead simian vector that entered phase I clinical trials in 2007 using the ME-TRAP insert.   Studies of correlates of immunity in both vaccinated and challenges volunteers and natural immunity in field studies have identified memory T cells to TRAP as a correlates of immunity in humans and the TRAP antigen has been found to be more immunogenic for T cell induction in clinical trial of vectored vaccines than the circumsporozoite protein.

Detailed studies of blood-stage antigens have shown that vectored vaccines can also induced substantial protection against blood-stage malaria when used in heterologous prime-boost regimes.  This protection is mediated by high titre antibodies against the blood-stage as well as T cell immune responses against the liver-stage parasite.  Clinical trials of blood-stage antigens in adenovirus and MVA vectors are planned for 2008 to evaluate this new approach.
Dr Hill’s immunogenetics programme currently focuses on genome-wide association studies of bacterial diseases, particularly tuberculosis and pneumococcal disease, and he is a participant in the Wellcome Trust case-control consortium that aims to identify new susceptibility genes using large scale approaches. 

Key publications
Schneider J, Gilbert SC, Blanchard TJ, Hanke T, Robson KJ, Hannan CM, Becker M, Sinden R, Smith GL, Hill AVS. (1998) Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara. Nature Medicine 4: 397-402.

McConkey SJ, Reece WHH, Moorthy VS, Webster, Dunachie S, Butcher G, Vuola JM, Blanchard TJ, Gothard P, Watkins K, Hannan CM, Everaere S, Brown K, Kester KE, Cummings J, Williams J, Heppner DG, Pathan A, Flanagan K, Arulanantham N, Roberts MTM, Roy M, Smith GL, Schneider J, Peto T, Sinden RE, Gilbert SC, Hill AVS (2003) Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humans. Nature Medicine 9: 729-735.

Reece WH, Pinder M, Gothard PK, Milligan P, Bojang K, Doherty T, Plebanski M, Akinwunmi P, Everaere S, Watkins KR, Voss G, Tornieporth N, Alloueche A, Greenwood BM, Kester KE, McAdam KP, Cohen J, Hill AVS (2004)  A CD4(+) T-cell immune response to a conserved epitope in the circumsporozoite protein correlates with protection from natural Plasmodium falciparum infection and disease. Nature Medicine 10:406-10.

Webster DP, Dunachie S, Vuola JM, Berthoud T, Keating S, Laidlaw SM, McConkey SJ, Poulton I, Andrews L, Andersen RF, Bejon P, Butcher G, Sinden R, Skinner MA, Gilbert SC, Hill AVS (2005). Enhanced T cell-mediated protection against malaria in human challenges using the recombinant poxviruses FP9 and MVA.Proceedings of the National Academy of Sciences USA 102:4836-41.

Dunachie SJ, Walther M, Epstein JE, Keating S, Berthoud T, Andrews L, Andersen RF, Bejon P, Goonetilleke N, Poulton I, Webster DP, Butcher G, Watkins K, Sinden RE, Levine GL, Richie TL, Schneider J, Kaslow D, Gilbert SC, Carucci DJ, Hill AVS. (2006) A DNA prime-modified vaccinia virus Ankara boost vaccine encoding thrombospondin-related adhesion protein but not circumsporozoite protein partially protects healthy malaria-naive adults against Plasmodium falciparum sporozoite challenge. Infection and Immunity 74:5933-42.

Bejon P, Ogada E, Mwangi T, Milligan P, Lang T, Fegan G, Gilbert SC, Peshu N, Marsh K, Hill AVS (2007). Extended follow-up following a phase 2b randomized trial of the candidate malaria vaccines FP9 ME-TRAP and MVA ME-TRAP among children in Kenya. PLoS ONE. Aug 15;2:e707

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