Malaria Programme: Pre-erythrocytic Vaccines
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.
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 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.
Adrian Hill, Programme Leader
Paulo Bettencourt, Post-doctoral scientist (pre-clinical)
Duncan Bellamy, Research Assistant
Thomas Broadhead, Insectary Technician
Georgina Bowyer, Research Assistant & DPhil Student
Mehreen Datoo, Clinical Research Fellow
Nick Edwards, Senior Research Assistant
Katie Ewer, Senior Immunologist (clinical trials)
Amy Flaxman, post-doctoral scientist (clinical trials)
Daniel Jenkins, Clinical Research Fellow
Alison Lawrie, Senior Vaccine Development Co-ordinator & Clinical Project Manager
Catherine Mair, Research Assistant
Richard Morter, IITM DPhil Student
Ian Poulton, Study Coordinator
Rachel Roberts, Malaria & Flu Vaccine Programme Coordinator
Ahmed Salman, Post-doctoral scientist (clinical trials)
Alex Spencer, Senior Immunologist (pre-clinical)
Marta Ulaszewska, Research Technician
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Ogwang, C., et al. Prime-boost vaccination with chimpanzee adenovirus and modified vaccinia Ankara encoding TRAP provides partial protection against Plasmodium falciparum infection in Kenyan adults. Sci Transl Med. 2015 May 6;7(286):286re5.
Kimani, D., et al., Translating the immunogenicity of prime-boost immunisation strategies from malaria naïve to malaria-endemic populations with ChAd63 and MVA ME-TRAP. Mol Ther. 2014 Jun 16. doi: 10.1038/mt.2014.109.
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