Adrian Hill

Adrian Hill is a Professor of Human Genetics at the Jenner Institute, University of Oxford. He 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.
Prof 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.