TY  - JOUR
AU  - Hodgson, SH
AU  - Ewer, KJ
AU  - Bliss, CM
AU  - Edwards, NJ
AU  - Rampling, T
AU  - Anagnostou, NA
AU  - de Barra, E
AU  - Havelock, T
AU  - Bowyer, G
AU  - Poulton, ID
AU  - de Cassan, S
AU  - Longley, R
AU  - Illingworth, JJ
AU  - Douglas, AD
AU  - Mange, PB
AU  - Collins, KA
AU  - Roberts, R
AU  - Gerry, S
AU  - Berrie, E
AU  - Moyle, S
AU  - Colloca, S
AU  - Cortese, R
AU  - Sinden, RE
AU  - Gilbert, SC
AU  - Bejon, P
AU  - Lawrie, AM
AU  - Nicosia, A
AU  - Faust, SN
AU  - Hill, AVS
Y2  - 2020/12/17
Y1  - 2015/04/01
SN  - 0022-1899
UR  - http://hdl.handle.net/11343/254780
AB  - 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.
LA  - English
PB  - OXFORD UNIV PRESS INC
T1  - Evaluation of the Efficacy of ChAd63-MVA Vectored Vaccines Expressing Circumsporozoite Protein and ME-TRAP Against Controlled Human Malaria Infection in Malaria-Naive Individuals
DO  - 10.1093/infdis/jiu579
IS  - Journal of Infectious Diseases
VL  - 211
IS  - 7
SP  - 1076-1086
L1  - /bitstream/handle/11343/254780/PMC4354983.pdf?sequence=1&isAllowed=y
ER  -