DIRECTOR OF THE JENNER INSTITUTE, LAKSHMI MITTAL & FAMILY PROFESSOR OF VACCINOLOGY, PROFESSOR OF HUMAN GENETICS
Adrian 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 the liver-stage of malaria.
To achieve greater levels of protective efficacy his group is currently developing more immunogenic prime-boost regimes involving recombinant chimpanzee adenoviruses as priming agents and MVA as a boosting agent. This type of regime has now shown excellent immunogenicity in over 20 clinical trials for malaria with significant efficacy. More immunogenic vectored vaccines are being developed using new internal adjuvants that work well in viral vectors, along with a range of new liver-stage target antigens. A very promising new virus-like particle vaccine, R21, has been developed as an a potentially improved version of the leading RTS,S vaccine candidate and this will be combined with viral vectors targeting the liver-stage in upcoming clinical trials.
In 2014 his group led the first clinical trial of a monovalent Ebola virus vaccine aimed at targeting the outbreak strain of Ebola virus in West Africa.
His immunogenetics programme includes genome-wide and exomic association studies of bacterial diseases, particularly tuberculosis, sepsis and pneumococcal disease. The group also has interests in susceptibility to Salmonella infections in Africa and to rheumatic heart disease in Pacific Islanders. A new programme is studying the genetic basis of variable responses to vaccination with several childhood vaccines.
Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial.
Emary KRW. et al, (2021), Lancet, 397, 1351 - 1362
Safety and Immunogenicity of Adenovirus and Poxvirus Vectored Vaccines against a Mycobacterium Avium Complex Subspecies
Folegatti PM. et al, (2021), Vaccines, 9, 262 - 262
Low immunogenicity of malaria pre-erythrocytic stages can be overcome by vaccination.
Müller K. et al, (2021), EMBO Mol Med
Mapping immune variation and var gene switching in naive hosts infected with Plasmodium falciparum
Milne K. et al, (2021), eLife, 10
Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials
Voysey M. et al, (2021), The Lancet, 397, 881 - 891