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. Pediatr Infect Dis J. 2018 Feb 09;: Authors: Witte D, Cunliffe NA, Turner AM, Ngulube E, Ofori-Anyinam O, Vekemans J, Chimpeni P, Lievens M, Wilson TP, Njiramʼmadzi J, Mendoza YG, Leach A Abstract BACKGROUND: In a phase III trial, the RTS,S/AS01 malaria vaccine produced lower anti-circumsporozoite (CS) antibody titres when co-administered with Expanded Programme on Immunisation (EPI) vaccines (0,1,2-month schedule) at 6-12 weeks compared to 5-17 months at first vaccination. Alternative infant immunisation schedules within the EPI were investigated. METHODS: This phase II, open, single site (Blantyre, Malawi) trial was conducted in infants aged 1-7 days. Subjects were equally randomised across seven groups to receive three doses of RTS,S/AS01E at time points that included ≤7 days, 6, 10, 14, 26 weeks, and 9 months. All RTS,S/AS01E groups plus a control group (without RTS,S/AS01E) received BCG+OPV at ≤7 days, DTPwHepB/Hib+OPV at 6,10,14 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; ELISA) 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 to control was observed. Compared to the standard 6,10,14 week schedule, anti-CS antibody GMC ratios post-Dose 3 were significantly higher in the 10,14,26 week group only (ratio 1.80; 95%CI:1.24, 2.60); RTS,S/AS01E vaccination at ≤7 days, 10,14 weeks produced significantly lower anti-CS GMCs (ratio 0.59; 95%CI:0.38, 0.92). CONCLUSIONS: Initiation of RTS,S/AS01E vaccination above six weeks of age tended to improve anti-CS antibody responses. Neonatal vaccination was well tolerated, but produced a comparatively lower immune response. REGISTRATION: Clinical Trials.gov identifier: NCT01231503GlaxoSmithKline Study ID number: 111315 (Malaria-057). PMID: 29432383 [PubMed – as supplied by publisher]

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Safety and Immunogenicity of Seven Dosing Regimens of the Candidate RTS,S/AS01E Malaria Vaccine Integrated within an Expanded Program on Immunization…