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.
Pre-clinical research
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.
Clinical trials
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.
Our team
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Adrian Hill
Director of the Jenner Institute, Lakshmi Mittal & Family Professor of Vaccinology, Professor of Human Genetics
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Mehreen Datoo
Clinical Research Fellow and DPhil Student
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Alison Lawrie
Senior Vaccine Development Co-ordinator & Head of Regulatory Affairs
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Ian Poulton
Research Nurse Manager
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Lisbeth Soederberg
EA to Professor Adrian Hill
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Lisa Stockdale
Head of Pre-erythrocytic Malaria Vaccine Immunology
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Amelia Bajer
Research Assistant
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Olivia Munoz
Post-doctoral Immunologist
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Samuel Provstgaard-Morys
DPhil Student
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Sophie Weston
Clinical Trials Project Manager
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Gulbuse Turan
DPhil Student
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Katerina Rapi
Research Assistant
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Ben Hollingdale
Research Assistant
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Shuyang (Sharon) Wu
DPhil Student
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Khojasteh Shirkhani
Project Manager
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Amy Flaxman
Senior Post-Doctoral Immunologist
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Zakia Alhareth
Post-Doctoral Researcher
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Penelope Saverton
Research Assistant
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Maria Miro Navarro
Research Assistant
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Alanna Kelly
Post-doctoral Immunologist
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Clement Twumasi
Medical Statistician
Selected publications
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CXCR3+ T Follicular Helper Cells Induced by Co-Administration of RTS,S/AS01B and Viral-Vectored Vaccines Are Associated With Reduced Immunogenicity and Efficacy Against Malaria
Journal article
Bowyer G. et al, (2018), Frontiers in Immunology, 9
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Assessment of novel vaccination regimens using viral vectored liver stage malaria vaccines encoding ME-TRAP
Journal article
Bliss CM. et al, (2018), Scientific Reports, 8
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Safety and Immunogenicity of Malaria Vectored Vaccines Given with Routine Expanded Program on Immunization Vaccines in Gambian Infants and Neonates: A Randomized Controlled Trial
Journal article
Mensah VA. et al, (2017), Frontiers in Immunology, 8
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Enhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccine
Journal article
Collins KA. et al, (2017), Scientific Reports, 7
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An in vitro assay to measure antibody-mediated inhibition of P. berghei sporozoite invasion against P. falciparum antigens
Journal article
Rodríguez-Galán A. et al, (2017), Scientific Reports, 7
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Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants
Journal article
Bliss CM. et al, (2017), Molecular Therapy, 25, 547 - 559
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The Threshold of Protection from Liver-Stage Malaria Relies on a Fine Balance between the Number of Infected Hepatocytes and Effector CD8+ T Cells Present in the Liver
Journal article
Spencer AJ. et al, (2017), The Journal of Immunology, 198, 2006 - 2016
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Adjuvanting a viral vectored vaccine against pre-erythrocytic malaria
Journal article
Milicic A. et al, (2017), Scientific Reports, 7
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Safety and High Level Efficacy of the Combination Malaria Vaccine Regimen of RTS,S/AS01BWith Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara Vectored Vaccines Expressing ME-TRAP
Journal article
Rampling T. et al, (2016), Journal of Infectious Diseases, 214, 772 - 781
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Comparative assessment of vaccine vectors encoding ten malaria antigens identifies two protective liver-stage candidates
Journal article
Longley RJ. et al, (2015), Scientific Reports, 5
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Prime-boost vaccination with chimpanzee adenovirus and modified vaccinia Ankara encoding TRAP provides partial protection against
Plasmodium falciparum
infection in Kenyan adults
Journal article
Ogwang C. et al, (2015), Science Translational Medicine, 7
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Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation
Journal article
Ewer KJ. et al, (2013), Nature Communications, 4