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

• Main Authors: Hodgson, S.H (Author), Ewer, K.J (Author), Bliss, C.M (Author), Edwards, N.J (Author), Rampling, T. (Author), Anagnostou, N.A (Author), de Barra, E. (Author), Havelock, T. (Author), Bowyer, G. (Author), Poulton, I.D (Author), de Cassan, S. (Author), Illingworth, J.J (Author), Douglas, A.D (Author), Mange, P.B (Author), Collins, K.A (Author), Roberts, R. (Author), Gerry, S. (Author), Berrie, E. (Author), Moyle, S. (Author), Colloca, S. (Author), Cortese, R. (Author), Sinden, R.E (Author), Gilbert, S.C (Author), Bejon, P. (Author), Lawrie, A.M (Author), Nicosia, A. (Author), Faust, S.N (Author), Hill, A.V (Author)
• Format: Article
• Language: English
• Published: 2015-04-01.
• Subjects: Article
• Online Access: Get fulltext

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. 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). 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. 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