Safety and efficacy of novel malaria vaccine regimens of RTS,S/AS01B alone, or with concomitant ChAd63-MVA-vectored vaccines expressing ME-TRAP

Efficacy of concomitant administration of RTS,S/AS01B with ChAd63-MVA ME-TRAP and RTS,S/AS01B immunization alone following Plasmodium falciparum 3D7 sporozoite challenge. Kaplan–Meier survival analyses. Log-rank test for significance. a Kaplan–Meier survival analysis of time to treatment following CHMI in individual groups. Mean time to diagnosis was 11.6 (±0.22) days for unvaccinated controls. All vaccine recipients were undiagnosed by day 23 after CHMI, or were diagnosed after the control mean？±？2？SD. b Kaplan–Meier survival analysis of time to treatment following CHMI in pooled vaccine groups. Vaccine recipients who had received a schedule consisting of RTS,S/AS01B alone (Groups 1 and 2) were pooled, and vaccine recipients who had received a schedule consisting of RTS,S/AS01B with viral vectors expressing ME-TRAP (Groups 3 and 4) were pooled. c Kaplan–Meier survival analysis of time to first sample with >20 parasites/mL detected by quantitative polymerase chain reaction (qPCR). Mean time to this endpoint was 8.9 (±0.89) days for unvaccinated controls. Seven out of eight subjects in Group 1 (87.5%), 9/9 (100%) subjects in Group 2, 9/10 (90%) subjects in Group 3, and 8/9 (88.9%) subjects in Group 4 did not reach this endpoint, or did so after the control mean？±？2？SD. d Kaplan–Meier survival analysis of time to first sample with >500 parasites/mL detected by qPCR. Mean time to this endpoint was 11.25 (±0.43) days for unvaccinated controls. Six out of eight subjects in Group 1 (75%), 9/9 (100%) subjects in Group 2, 7/10 (70%) subjects in Group 3, and 8/9 (88.9%) did not reach this endpoint, or did so after the control mean？±？2？SD. R-R-R, three standard doses (50？μg) of RTS,S/AS01B delivered at 4-week intervals; R-R-r, two standard doses (50？μg) of RTS,S/AS01B followed by a fractional third dose (10？μg). Vaccines delivered at 4-week intervals; RA-RM-RM, three standard doses (50？μg) of RTS,S/AS01B delivered at 4-week intervals with concomitant administration of Chimpanzee adenovirus 63 (ChAd63) expressing multiple-epitope thrombospondin-related adhesion protein (ME-TRAP) at week 0, and modified vaccinia Ankara (MVA) expressing ME-TRAP at weeks 4 and 8; RA-RM-rM, two standard doses (50？μg) of RTS,S/AS01B followed by a fractional third dose (10？μg) with concomitant administration of ChAd63 ME-TRAP at week 0, and MVA ME-TRAP at weeks 4 and