Malaria Programme: Blood-stage Vaccines

Pre-clinical research

The pre-clinical research undertaken in the group focuses on the development of novel and improved approaches to blood-stage malaria vaccine design, as well as aiming to better understand mechanisms of vaccine-induced immunity to blood-stage malaria infection. This work has a number of important goals:

1. Improving antibody induction by human-compatible subunit vaccine platforms – including both viral vectored and protein- adjuvant vaccine delivery systems.
2. Improving our understanding of antibody and B cell induction by subunit vaccine delivery platforms.
3. Antigen-screening to define optimal target combinations that neutralise blood-stage malaria parasites, and the development of new candidate vaccines capable of delivering these targets.
4. Improving our understanding of how vaccine-induced immune effector mechanisms can control or eliminate blood-stage malaria parasites.

Alongside basic research, there is a strong translational emphasis, with the most promising new approaches and/or candidate vaccines feeding into the clinical trials programme. The work undertaken by this group has so far led to four Phase I/IIa clinical trials in Oxford.

Clinical trials

The blood-stage malaria group has so far undertaken four Phase I/IIa clinical trials in Oxford. We have developed simian adenovirus (ChAd63) and MVA viral vectored vaccines targeting two major candidate antigens from the human malaria parasite P. falciparum (MSP1 and AMA1), and have demonstrated potent and effective T cell and antibody immunogenicity in pre-clinical models. We have translated these findings into Phase I/IIa clinical vaccine trials funded by the MRC and EMVDA. The aims of this work are to assess the safety, immunogenicity and protective efficacy of these new vaccines in human volunteers.

Current trials are seeking to assess whether improved antibody responses can be achieved in healthy adult volunteers immunised with the ChAd63 and MVA vectors encoding AMA1, when these are combined with a protein AMA1 vaccine formulated with Alhydrogel ± CpG adjuvant. Future trials will also test the safety and immunogenicity of new ChAd63 and MVA candidate vaccines encoding the PvDBP_RII antigen from P. vivax malaria.

These studies also provide an opportunity to better understand how vaccine-induced responses can protect against malaria infection in humans, and also how exposure to the parasite can modulate immunity. We have a particular interest in B cells and how antibodies interact with immune cells in humans via Fc-receptors. These studies of malaria-exposed volunteers in Oxford are also complemented by similar immunological studies in individuals who are naturally-exposed to malaria in Africa through our collaboration with the KEMRI-Wellcome Institute in Kilifi, Kenya.

These are the blood-stage malaria clinical trials currently in progress:

Vac044 Phase Ia safety & immunogenicity of ChAd63-MVA AMA1 combined with AMA1-C1 protein vaccine formulated with Alhydrogel ± CpG adjuvant NCT01351948

Vac039 Phase IIa safety, immunogenicity & efficacy of ChAd63-MVA AMA1 ± MSP1 NCT01142765

Vac037 Phase I/IIa safety, immunogenicity & efficacy of ChAd63-MVA MSP1 NCT01003314

Vac036 Phase Ia safety & immunogenicity of ChAd63-MVA AMA1 NCT01095055

Group members:

Simon Draper, Group Leader
Sumi Biswas, Postdoctoral Scientist
Simone de Cassan, Postdoctoral Scientist
Andrew Williams, Postdoctoral Scientist & Insectary Manager
Susanne Sheehy, Clinical Research Fellow
Sandy Douglas, DPhil student
Sean Elias, DPhil student
Joe Illingworth, DPhil student
David Llewellyn, DPhil student
Prateek Choudhary, Clinical Trials Research Assistant
Sara Zakutansky, Parasitology Research Assistant

Publications

Biswas, S., A.J. Spencer, E.K. Forbes, S.C. Gilbert, A.A. Holder, A.V.S. Hill, & S.J. Draper. Recombinant viral vectored vaccines expressing Plasmodium chabaudi AS apical membrane antigen 1: Mechanisms of vaccine-induced blood-stage protection. J Immunol, 2012. [Pubmed]

Duncan, C.J.A, & S.J. Draper. Controlled human blood-stage malaria infection: current status and potential applications. Am J Trop Med Hyg, 2012. 86(4): p. 561-5. [Pubmed]

Sheehy, S.H, C.J.A. Duncan, S.C. Elias, S. Biswas, K.A. Collins, G.A. O’Hara, F.D. Halstead, K.J. Ewer, T. Mahungu, A.J. Spencer, K. Miura, I.D. Poulton, M.D.J. Dicks, N.J. Edwards, E. Berrie, S. Moyle, S. Colloca, R. Cortese, K. Gantlett, C.A. Long, A.M. Lawrie, S.C. Gilbert, T. Doherty, A. Nicosia, A.V.S. Hill, & S.J. Draper. Phase Ia Clinical Evaluation of the Safety and Immunogenicity of the Plasmodium falciparum Blood-Stage Antigen AMA1 in ChAd63 and MVA Vaccine Vectors. PLoS One, 2012. 7(2): p. e31208. [Pubmed]

Douglas, A.D., A.R. Williams, J.J. Illingworth, G. Kamuyu, S. Biswas, A.L. Goodman, D.H. Wyllie, C. Crosnier, K. Miura, G.J. Wright, C.A. Long, F.H. Osier, K. Marsh, A.V. Turner, A.V.S. Hill, & S.J. Draper. The Blood-Stage Malaria Antigen PfRH5 is Susceptible to Vaccine-Inducible Cross-Strain Neutralizing Antibody. Nat Commun, 2011. 2: p. 601. [Pubmed]

Goodman, A.L., A.M. Blagborough, S. Biswas, Y. Wu, A.V.S. Hill, R.E. Sinden, & S.J. Draper. A viral vectored prime-boost immunization regime targeting the malaria Pfs25 antigen induces transmission-blocking activity. PLoS One, 2011. 6(12): p. e29428. [Pubmed]

Bregu, M., S.J. Draper, A.V.S. Hill, & B.M. Greenwood. Accelerating vaccine development and deployment: report of a Royal Society satellite meeting. Philos Trans R Soc Lond B Biol Sci, 2011. 366(1579): p. 2841-9. [Pubmed]

Sheehy, S.H., C.J.A. Duncan, S.C. Elias, K.A. Collins, K.J. Ewer, A.J. Spencer, A.R. Williams, F.D. Halstead, S.E. Moretz, K. Miura, C. Epp, M.D.J. Dicks, I.D. Poulton, A.M. Lawrie, E. Berrie, S. Moyle, C.A. Long, S. Colloca, R. Cortese, S.C. Gilbert, A. Nicosia, A.V.S. Hill, & S.J. Draper. Phase Ia Clinical Evaluation of the Plasmodium falciparum Blood-stage Antigen MSP1 in ChAd63 and MVA Vaccine Vectors. Mol Ther, 2011. 19(12): p. 2269-76. [Pubmed]