Malaria Vaccine Programme

Programme Leader: Prof Adrian Hill

The programme of pre-clinical malaria vaccine development at Oxford has led to significant advances in the field of vectored vaccines. This work began with a primary interest in the induction of high level T cell responses against pre-erythrocytic liver-stage malaria antigens, but this has widened more recently to also include high level antibody induction against the blood-stage.

Malaria vaccine development at the Jenner Institute is divided into three main areas:

1. Pre-erythrocytic Vaccines

2. Blood-stage Vaccines

3. Transmission-blocking Vaccines

Malaria kills around 0.8 million individuals per annum, mostly in sub-Saharan Africa where 1 in 5 childhood deaths is associated with malaria. Developing a vaccine against malaria has been difficult due to the ever changing nature of the parasite in terms of its genetic diversity and life-cycle. While natural protection is developed over many years of exposure, a clear immunological correlate of protection has yet to be identified, potentially owing to the fact that a different type of immune response is required for each stage of the malaria life-cycle.

Distribution of malaria around the world
Map showing distribution of malaria around the world. Source: Genome Research Limited.

Prime-boost immunisation regimes

Early studies in this group led to the development of heterologous prime-boost immunisation regimes using DNA and MVA vaccine vectors. These regimes, capable of inducing unprecedented levels of CD8+ and CD4+ T cell immunogenicity, were developed to target the liver-stage antigens ME-TRAP and CSP, and could induce high levels of protective efficacy in pre-clinical models of liver-stage malaria.

Heterologous prime-boost immunisation regimes are now being developed in labs around the world to target many difficult diseases, including HIV and TB, where strong cellular immune responses are required for protection. Subsequent studies led to the development of heterologous poxvirus FP9-MVA immunisation regimes, and more recently the use of adenovirus vectors (of both human and simian serotype) deployed either alone or with an MVA boost.