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

Paulo Bettencourt, Postdoc

Carly Bliss, Research Assistant & DPhil Student

Georgina Bowyer, Research Assistant 

Nick Edwards, Senior Research Assistant

Katie Ewer, Senior Immunologist

Benedict Halbroth, DPhil student

Anita Gola, DPhil student

Christos Krastev, DPhil student

Alison Lawrie, Senior Vaccine Development Co-ordinator & Clinical Project Manager

Ian Poulton, Study Coordinator

Jonathan Powlson, Research Assistant

Rachel Roberts, Malaria & Flu Vaccine Programme Coordinator

Ahmed Salman, Post-Doc

Alex Spencer, Senior Immunologist

Marta Ulaszewska, Research Technician

Adam Walters, Research Assistant

Publications

Rampling, T., et al. Safety and High Level Efficacy of the Combination Malaria Vaccine Regimen of RTS,S/AS01B With Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara Vectored Vaccines Expressing ME-TRAP. J Infect Dis. 2016 Sep 1;214(5):772-81. 

Ewer, KJ., et al. Viral vectors as vaccine platforms: from immunogenicity to impact. Curr Opin Immunol. 2016 Aug;41:47-54. 

Longley, RJ., et al. Comparative assessment of vaccine vectors encoding ten malaria antigens identifies two protective liver-stage candidates. Sci Rep. 2015 Jul 3;5:11820.

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.  

Ewer, KJ., et al. Progress with viral vectored malaria vaccines: A multi-stage approach involving "unnatural immunity". Vaccine. 2015 Dec 22;33(52):7444-51.

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.

Ewer, KJ., et al., Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation. Nat Commun. 2013;4:2836. doi: 10.1038/ncomms3836.

O'Hara, GA., et al., Clinical assessment of a recombinant simian adenovirus ChAd63: a potent new vaccine vector. J Infect Dis. 2012 Mar 1;205(5):772-81. Epub 2012 Jan 24.