Malaria Programme: Pre-erythrocytic Vaccines

Pre-clinical research

The pre-clinical research of this group is aimed towards developing 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:

1. Improving and optimising T cell inducing vaccines against the liver-stage of malaria.
2. Improving and understanding antibody based vaccines against the sporozoite stage of malaria.
3. Screening of new liver-stage malaria antigens for the ability of T cells to kill malaria infected hepatocytes.
4. Improving our understanding of the immune response to the pre-erythrocytic stage of malaria.

Clinical trials

The malaria vaccine programme at Oxford is a linked pre-clinical and clinical vaccine development programme that has primarily targeted 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 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.

Group Members

Adrian Hill, Programme Leader
Katie Ewer, Senior Immunologist
Arturo Reyes-Sandoval, Postdoc
Alex Spencer, Postdoc
Karolis Bauza, DPhil student
Katharine Collins, DPhil student
Alison Lawrie, Senior Vaccine Development Co-ordinator & Clinical Project Manager
Rhea Longley, DPhil student
Anita Milicic, Adjuvant Bank Manager
Ian Poulton, Study Coordinator
Rachel Roberts, Malaria & Flu Vaccine Programme Coordinator

Publications

Reyes-Sandoval, A., S. Sridhar, T. Berthoud, A. C. Moore, J. T. Harty, S. C. Gilbert, G. Gao, H. C. Ertl, J. C. Wilson, and A. V. Hill. 2008. Single-dose immunogenicity and protective efficacy of simian adenoviral vectors against Plasmodium berghei. Eur J Immunol 38:732-741.

Reyes-Sandoval, A., T. Berthoud, N. Alder, L. Siani, S. C. Gilbert, A. Nicosia, S. Colloca, R. Cortese, and A. V. Hill. 2010. Prime-boost immunization with adenoviral and modified vaccinia virus Ankara vectors enhances the durability and polyfunctionality of protective malaria CD8+ T-cell responses. Infect Immun 78:145-153.