Evaluation of the efficacy of ChAd63-MVA vectored vaccines expressing CS & ME-TRAP against controlled human malaria infection in malaria naïve individuals

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Hodgson, S.H. ; Ewer, K.J. ; Bliss, C.M. ; Edwards, N.J. ; Rampling, T. ; Anagnostou, N.A. ; de Barra, E. ; Havelock, T. ; Bowyer, G. ; Poulton, I.D. ; de Cassan, S. ; Illingworth, J.J. ; Douglas, A.D. ; Mange, P.B. ; Collins, K.A. ; Roberts, R. ; Gerry, S. ; Berrie, E. ; Moyle, S. ; Colloca, S. ; Cortese, R. ; Sinden, R.E. ; Gilbert, S.C. ; Bejon, P. ; Lawrie, A.M. ; Nicosia, A. ; Faust, S.N . ; Hill, A.V. (2015)

Background.?Circumsporozoite protein (CS) is the antigenic target for RTS,S, the most advanced malaria vaccine to date. Heterologous prime-boost with the viral vectors ChAd63-MVA is the most potent inducer of T-cells in humans, demonstrating significant efficacy when expressing the pre-erythrocytic antigen insert ME-TRAP. We hypothesised that ChAd63-MVA containing CS may result in significant, clinical protective efficacy.<br/><br/>Methods.?We conducted an open-label, two-site partially randomized sporozoite controlled human malaria infection (CHMI) study to compare the clinical efficacy of ChAd63-MVA CS with ChAd63-MVA ME-TRAP. The study was registered at: www.clinicaltrials.gov (NCT01623557).<br/><br/>Results.?1/15 (7%) vaccinees receiving ChAd63-MVA CS and 2/15 (13%) vaccinees receiving ChAd63-MVA ME-TRAP were sterilely protected post-CHMI. 3/15 (20%) vaccinees receiving ChAd63-MVA CS and 5/15 (33%) vaccinees receiving ChAd63-MVA ME-TRAP demonstrated a delay in time to treatment compared to unvaccinated controls. In qPCR analyses, ChAd63-MVA CS was estimated to reduce liver parasite burden by 69-79%, compared to 79-84% for ChAd63-MVA ME-TRAP.<br/><br/>Conclusions.?ChAd63-MVA CS does result in a reduction in liver parasite burden but ChAd63-MVA ME-TRAP remains the most promising antigenic insert for a vectored liver-stage vaccine. Detailed analyses of parasite kinetics may allow detection of smaller, but biologically important differences in vaccine efficacy that can influence future vaccine development
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