An effective and highly efficacious malaria vaccine is required to help reduce the burden of malaria in endemic countries. Since 2003, EDCTP has supported six projects that include clinical trials of vaccines and projects that have a focus on immunological responses and capacity building for vaccine trials.

Among these projects are the studies of the Malaria Vectored Vaccine Consortium (MVVC) led by Dr Odile Leroy from the European Vaccine Initiative in Germany. It aims to develop a liver stage malaria vaccine based on the thrombospondine-related adhesion protein (TRAP) that is fused to a string of multiple T cell epitopes (ME) administered in two different viral vectors.

TRAP is an abundant parasite surface protein that is expressed in the early life cycle stages, the sporozoites and the liver stages. The two viral vectors ChAd63 (a simian adenovirus vector) and MVA (Modified Vaccinia Ankara) both express ME-TRAP and are administered in a prime-boost regimen, which aims to provoke a strong cellular immune response directed against TRAP.

Pre-clinical studies, as well as early phase clinical trials, provided evidence that the prime-boost regimen with Chad63 and MVA viral vectors induced strong CD8 T cell responses shown to be protective against malaria in human challenge trials.

An effective vaccine targeting the malaria liver stages has the potential to prevent the disease as it would eliminate the parasite before it multiplies in the red blood cells. The prime-boost approach based on viral vectors is targeting the T cell immune pathway, similar to the immune response induced by the pathogen in the human host. With only two doses, the prime-boost approach would also simplify the paediatric vaccine schedule, and could ultimately reduce the costs of malaria vaccination.

The MVVC study showed good safety and immunogenicity in adults in phase Ib clinical trials conducted in The Gambia and in Kenya, as well as in Gambian children and infants. Furthermore, data obtained from a phase II clinical trial study in Kenya demonstrated that 67% protective efficacy against infection with Plasmodium falciparum can be achieved with a promising T cell-inducing vaccination strategy among adults living in a malaria-endemic area in the country.

The phase II clinical trial was conducted at the Kenya Medical Research Institute (KEMRI) field site located in Junju, Kilifi County, Kenya. Healthy adult male volunteers were randomly allocated to vaccination with either the T cell–inducing vaccine candidates or a control vaccine. Antimalarials were given to clear parasitaemia and frequent blood tests were done to identify new infections with the malaria parasite P. falciparum. Encouragingly, the researchers found that the volunteers receiving the T cell-inducing vaccine had a 67% reduction in the risk of malaria infection during 8 weeks of follow-up.

In a follow-up project (MVVC2), also supported by EDCTP, the consortium carried a phase I trial (VAC058) to assess the safety and immunogenicity of ChAd63 ME-TRAP–MVA ME-TRAP heterologous prime-boost vaccination co-administered with EPI vaccines in Gambian infants. Final results for this component are expected soon.

In addition, the consortium planned to conduct a phase Ib randomised, controlled, single- blind trial (VAC060) to assess the safety, immunogenicity of the Malaria Vaccine Candidate R21 with Matrix-M1 adjuvant in adult volunteers in Burkina Faso. After review of data from safety studies conducted in non-endemic settings, the trial has been initiated with first-subject-first-dose planned for 25 August 2016.

Relevant publication:

1. Ogwang, C; Kimani, D; Edwards, NJ; Roberts, R; Mwacharo, J; Bowyer, G; Bliss, C; Hodgson, SH; Njuguna, P; Viebig, NK; Nicosia, A; Gitau, E; Douglas, S; Illingworth, J; Marsh, J; Lawrie, A; Imoukhuede, EB; Ewer, K; Urban, BC; Hill, AVS; Bejon, P; the MVVC group. (2015) ‘Prime-boost vaccination with chimpanzee adenovirus and modified vaccinia Ankara encoding TRAP provides partial protection against Plasmodium falciparum infection in Kenyan adults’. Science Translational Medicine, 7(286):286re5.
2. Ogwang, C; Afolabi, M; Kimani, D; Jagne, YJ; Sheehy, SH; Bliss, CM; Duncan, CJ; Collins, KA; Garcia Knight, MA; Kimani, E; Anagnostou, NA; Berrie, E; Moyle, S; Gilbert, SC; Spencer, AJ; Soipei, P; Mueller, J; Okebe, J; Colloca, S; Cortese, R; Viebig, NK; Roberts, R; Gantlett, K; Lawrie, AM; Nicosia, A; Imoukhuede, EB; Bejon, P; Urban, BC; Flanagan, KL; Ewer, KJ; Chilengi, R; Hill, AV; Bojang, K. (2013) ‘Safety and immunogenicity of heterologous prime-boost immunisation with Plasmodium falciparum malaria candidate vaccines, ChAd63 ME-TRAP and MVA ME-TRAP, in healthy Gambian and Kenyan adults. PLOS ONE. 8(3):e57726.
3. Muhammed O Afolabi, Alfred B Tiono, Uche J Adetifa, Jean Baptiste Yaro, Abdoulie Drammeh, Issa Nébié, Carly Bliss, Susanne H Hodgson, Nicholas A Anagnostou, Guillaume S Sanou, Ya Jankey Jagne, Oumarou Ouedraogo, Casimir Tamara, Nicolas Ouedraogo, Mirielle Ouedraogo, Jainaba Njie-Jobe, Amidou Diarra, Christopher JA Duncan, Riccardo Cortese, Alfredo Nicosia, Rachel Roberts, Nicola K Viebig, Odile Leroy, Alison M Lawrie, Katie L Flanagan, Beate Kampman, Philip Bejon, Egeruan B Imoukhuede, Katie J Ewer, Adrian VS Hill, Kalifa Bojang and Sodiomon B Sirima, ‘Safety and Immunogenicity of ChAd63 and MVA ME-TRAP in West African Children and Infants’, Molecular Therapy advance online publication 28 June 2016; doi: 10.1038/mt.2016.83