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 . and Hill, A.V. (2015) Evaluation of the efficacy of ChAd63-MVA vectored vaccines expressing CS & ME-TRAP against controlled human malaria infection in malaria naïve individuals. The Journal of Infectious Diseases, 211 (7), 1076-1086. (doi:10.1093/infdis/jiu579). (PMID:25336730)
Abstract
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
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