Malaria Programme: Pre-erythrocytic Vaccines
The malaria vaccine programme at Oxford is a linked pre-clinical and clinical vaccine development programme, facilitating rapid translation of new vaccine candidates and technologies from the bench to the clinic.
Our pre-clinical research aims to develop new and improved vaccines/vaccination regimes against malaria from the point of injection of parasites from an infected mosquito to the emergence of blood-stage parasites from the liver. In addition we aim to better understand the natural and vaccine-induced immune response during this stage of malaria.
Our key areas of research include:
- Improving and optimising T cell inducing vaccines against the liver-stage of malaria.
- Improving and understanding antibody-based vaccines against the sporozoite stage of malaria.
- Screening of new liver-stage malaria antigens for the ability of T cells to kill malaria infected hepatocytes.
- Improving our understanding of the immune response to the pre-erythrocytic stage of malaria.
The early period of our clinical program primarily focussed on the induction of high level T cell responses against pre-erythrocytic antigens. We undertook the first prophylactic DNA vaccine trials in Europe and showed that DNA administered by needle or by gene gun generated only moderate immunogenicity and was not protective. Since these first clinical trials we have consistently translated our pre-clinical testing and demonstrated an increase in immunogenicity with development of new vectored vaccine platforms. Our most promising vaccine regime to date is the use of a simian Adenoviral vaccine expressing METRAP in combination with a modified Ankara virus (MVA) boost which induces some of the strong T cells responses observed to date.
Our current clinical trials are aimed at assessing novel antigens or vaccination regimes to maximise the breadth, quality and quantity of the immune response to pre-erythrocytic malaria. In addition we have undertaken a number of Phase IIb trials occurring in both West and East Africa to investigate the immunogenicity and efficacy of our leading clinical candidate vaccine combination. All of these clinical trials present the unique opportunity to understand vaccine induced immune responses and type of immune response required for protection against malaria.
More recently, we have developed a highly immunogenic virus-like particle vaccine to target the sporozoite stage of the malaria life-cycle. This new vaccine, known as R21, induces anti-sporozoite antibodies and has shown a high level of protective efficacy in a mouse model. R21 is now under evaluation in a number of Phase 1/2a clinical trials.
Additionally, we have an active immunology research program looking at mechanisms determining sub-optimal immunogenicity of vaccines in different regimes and populations.