Evaluation of the Efficacy of ChAd63-MVA Vectored Vaccines Expressing Circumsporozoite Protein and ME-TRAP Against Controlled Human Malaria Infection in Malaria-Naive Individuals
AuthorHodgson, SH; Ewer, KJ; Bliss, CM; Edwards, NJ; Rampling, T; Anagnostou, NA; de Barra, E; Havelock, T; Bowyer, G; Poulton, ID; ...
Source TitleJournal of Infectious Diseases
PublisherOXFORD UNIV PRESS INC
University of Melbourne Author/sLongley, Rhea
AffiliationMedical Biology (W.E.H.I.)
Document TypeJournal Article
CitationsHodgson, 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 StatusOpen Access
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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