As temporary freezing might have
reduced the potency of the vaccine, these subjects were excluded from participating in the malaria challenge. Of the 43 subjects enrolled, the mean age was 34.2 years (range: 20–45 years), 61% were males and the majority were Caucasian (49%) or African–American (40%). Transient pain at the injection site was the most frequently reported solicited local AE across vaccine groups in both studies, occurring with a similar incidence in each vaccine group (after 87–100% of doses) (Table 1). The frequency of Grade 3 pain was similar after vaccination across vaccine groups and studies (after 17–35% of doses). Grade 3 redness and swelling occurred after <7% of doses in any vaccine group. All Grade 3 AEs resolved within the initial 72-h Paclitaxel follow-up period after each vaccination, with the majority of symptoms resolved within the first 24 h. The most frequently reported solicited general symptom in the Phase 1 study was myalgia (after 47–63% of doses across groups) and in the Phase 2 study fatigue (after 30–32% of doses across groups). Grade 3 general AEs occurred after <7% of doses in any vaccine group. In the Phase 1 study
all Grade 3 symptoms were considered to have a ‘probable’/‘suspected’ (PB/SU) relationship to vaccination and in the Phase 2 study, one report of Grade 3 malaise in a recipient of RTS,S + TRAP/AS02 was judged to have a PB/SU relationship to vaccination. Unsolicited AEs with a PB/SU relationship to vaccination
PLK inhibitor were infrequent: influenza-like symptoms in 7 subjects (2 TRAP/AS02, 1 RTS,S/AS02, 4 RTS,S + TRAP/AS02), rigors in 1 subject (RTS,S + TRAP/AS02) and hypesthesia (numbness aminophylline of arm lasting 2 days) in 1 subject (RTS,S + TRAP/AS02) in the Phase 1 study; flu-like symptoms in 1 subject (RTS,S + TRAP/AS02) and upper respiratory tract infection in 1 subject (RTS,S + TRAP/AS02) in the Phase 2 study. No unsolicited AE with a PB/SU relationship to vaccination was of Grade 3 intensity. In both studies, no SAE was reported and no subject was withdrawn because of an AE. No clinically significant hematological, biochemical, or urine abnormalities were observed. In both studies, prior to vaccination, no volunteer had anti-CS antibodies (Table 2). In the Phase 1 study, the post immunization anti-CS GMTs at each timepoint were higher, but not statistically so, after administration of RTS,S/AS02 compared to RTS,S + TRAP/AS02. Post Dose 2, the anti-CS GMT in the RTS,S/AS02 group (85 μg/mL [95% CI: 53, 138]) tended to be higher than the RTS,S + TRAP/AS02 group (56 μg/mL [95% CI: 31, 100]) and higher than that of the corresponding Phase 2 post Dose 2 anti-CS GMT in the RTS,S + TRAP/AS02 group (35 μg/mL [95% CI: 20, 62]). In the Phase 1 study, an increase in anti-TRAP GMTs was observed after subsequent doses of TRAP/AS02 and RTS,S + TRAP/AS02 (Table 3); GMTs were similar in both groups.