Safety and Immunogenicity of Seven Dosing Regimens of the Candidate RTS, S/AS01E Malaria Vaccine Integrated Within an Expanded Program on Immunization Regimen: A Phase II, Single-Center, Open, Controlled Trial in Infants in Malawi. Issue 5 (May 2018) - Witte, Desiree
Abstract : Background: In a phase III trial, the RTS, S/AS01 malaria vaccine produced lower anti-circumsporozoite (CS) antibody titers when co-administered with Expanded Programme on Immunization vaccines (0-, 1- and 2-month schedule) at 6 to 12 weeks compared with 5 to 17 months at first vaccination. Alternative infant immunization schedules within the Expanded Programme on Immunization were investigated. Methods: This phase II, open, single-site (Blantyre, Malawi) trial was conducted in infants 1 to 7 days of age. Subjects were equally randomized across 7 groups to receive 3 doses of RTS, S/AS01E at time points that included ⩽7 days, 6, 10, 14 and 26 weeks, and 9 months. All RTS, S/AS01E groups plus a control group (without RTS, S/AS01E ) received Bacillus Calmette-Guérin + oral poliovirus vaccine at ⩽7 days, diphtheria, tetanus, whole-cell pertussis, hepatitis B and Haemophilus influenzae type b vaccine + oral poliovirus vaccine at 6, 10, and 14 weeks and measles vaccine at 9 months; one RTS, S/AS01E group and the control additionally received hepatitis B vaccination at ⩽7 days. Serum anti-CS antibody geometric mean concentration (GMC; enzyme-linked immunosorbent assay) and safety were assessed up to age 18 months. Results: Of the 480 infants enrolled, 391 completed the study. No causally related serious adverse event was reported. A higher frequency of fever within 7 days of RTS, S/AS01E vaccination compared with control was observed. Compared with the standard 6-, 10-, 14-week schedule, anti-CS antibody GMC ratios post-dose 3 were significantly higher in the 10-, 14- and 26-week group only (ratio 1.80; 95% confidence interval, 1.24–2.60); RTS, S/AS01E vaccination at ⩽7 days and 10 and 14 weeks produced significantly lower anti-CS GMCs (ratio 0.59; 95% confidence interval, 0.38–0.92). Conclusions: Initiation of RTS, S/AS01E vaccination above 6 weeks of age tended to improve anti-CS antibody responses. Neonatal vaccination was well tolerated but produced a comparatively lower immune response. Abstract : Supplemental Digital Content is available in the text.