Malaria transmission is falling in some parts of Africa as bed nets and anti-malarials become more widely available. However, transmission still persists and it appears that additional control measures are required. The leading malaria vaccine candidate in development is RTS,S which has efficacy against clinical malaria measured at 30-50% in the field. This partial protection might be enhanced by combination with other components. The other vaccination approach that has produced repeatable efficacy in humans is the use of viral vectors to induce T cell responses. Previous attempts with this vaccine approach have been effective in challenge studies in Oxford, but ineffective in the field, probably because of reduced immunogenicity with previous vector platforms.

Recently, studies in Oxford, Kenya and the Gambia have shown higher levels of immunogenicity by using a chimpanzee adenovirus (ChAd63) followed by an attenuated vaccinia virus (modified vaccinia Ankara) to deliver the pre-erythrocytic antigen, multiple epitope string with thrombospondin- related adhesion protein (ME-TRAP).

The increase in immunogenicity has lead to sterile protection in 3 out of 14 volunteers and partial protection in 5 out of 14 volunteers in challenge studies.

The investigators propose a Phase 2b study of 120 healthy adult men in Senegal. The investigators will assess the efficacy and further evaluate the immunogenicity and safety profile of the vaccine regimen. The investigators also intend to assess the correlates of efficacy and natural immunity.

Inclusion Criteria:

• Consenting adult males aged 18 - 50 years in good health.
• Will remain resident in the study area for the study duration.
• Able and willing (in the Investigator's opinion) to comply with all study requirements
• Informed Consent

Exclusion Criteria:

• Any significant medical disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data
• Hypersensitivity to HDCRV,the trial vaccines or the antimalarial used.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, e.g. egg products, kathon, neomycin
• History of splenectomy.
• Haemoglobin less than 10.0 g/dl
• Clinically significant abnormalities of laboratory screening tests (full blood count, ALT, creatinine levels).
• Blood transfusion within the month preceding enrolment.
• History of vaccination with previous experimental malaria vaccines or other vaccines likely to impact on findings of study (e.g. other MVA or adenovirus vectored vaccines)
• Administration of any other vaccine or immunoglobulin within 2 weeks before vaccination.

HIV or Hepatitis B surface antigen seropositivity.

• Current participation in another clinical trial or recent participation within 12 weeks of this study.
• Any other finding which in the opinion of the investigators would increase the risk of an adverse outcome from participation in the trial.
• Likelihood of travel away from the study area