Evaluation of the Efficacy of ChAd63-MVA Vectored Vaccines Expressing Circumsporozoite Protein and ME-TRAP Against Controlled Human Malaria Infection in Malaria-Naive Individuals

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Hodgson, SH; Ewer, KJ; Bliss, CM; Edwards, NJ; Rampling, T; Anagnostou, NA; de Barra, E; Havelock, T; Bowyer, G; Poulton, ID; ...Date
2015-04-01Source Title
Journal of Infectious DiseasesPublisher
OXFORD UNIV PRESS INCUniversity of Melbourne Author/s
Longley, RheaAffiliation
Medical Biology (W.E.H.I.)Metadata
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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., Longley, R., Illingworth, J. J., Douglas, A. D., Mange, P. B., Collins, K. A., Roberts, R., Gerry, S., Berrie, E. ,... Hill, A. V. S. (2015). Evaluation of the Efficacy of ChAd63-MVA Vectored Vaccines Expressing Circumsporozoite Protein and ME-TRAP Against Controlled Human Malaria Infection in Malaria-Naive Individuals. JOURNAL OF INFECTIOUS DISEASES, 211 (7), pp.1076-1086. https://doi.org/10.1093/infdis/jiu579.Access Status
Open AccessAbstract
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 simian adenovirus 63 (ChAd63)-modified vaccinia virus Ankara (MVA) is the most potent inducer of T-cells in humans, demonstrating significant efficacy when expressing the preerythrocytic antigen insert multiple epitope-thrombospondin-related adhesion protein (ME-TRAP). We hypothesized that ChAd63-MVA containing CS may result in a significant clinical protective efficacy. METHODS: We conducted an open-label, 2-site, partially randomized Plasmodium falciparum sporozoite controlled human malaria infection (CHMI) study to compare the clinical efficacy of ChAd63-MVA CS with ChAd63-MVA ME-TRAP. RESULTS: One of 15 vaccinees (7%) receiving ChAd63-MVA CS and 2 of 15 (13%) receiving ChAd63-MVA ME-TRAP achieved sterile protection after CHMI. Three of 15 vaccinees (20%) receiving ChAd63-MVA CS and 5 of 15 (33%) receiving ChAd63-MVA ME-TRAP demonstrated a delay in time to treatment, compared with unvaccinated controls. In quantitative polymerase chain reaction analyses, ChAd63-MVA CS was estimated to reduce the liver parasite burden by 69%-79%, compared with 79%-84% for ChAd63-MVA ME-TRAP. CONCLUSIONS: ChAd63-MVA CS does reduce the 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. CLINICAL TRIALS REGISTRATION: NCT01623557.
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