Evaluation of the Safety and Immunogenicity of the RTS,S/AS01_EMalaria Candidate Vaccine When Integrated in the Expanded Program of Immunization

Abstract

RTS,S/AS01(E) integrated in the EPI showed a favorable safety and immunogenicity evaluation. Trial registration. ClinicalTrials.gov identifier: NCT00436007 . GlaxoSmithKline study ID number: 106369 (Malaria-050).

The RTS,S/AS01 malaria vaccine in children 5 to 17 months of age at first vaccination

“…The potential of the RTS,S/ AS01 vaccine to predispose to humoral hypo-responsiveness to CS by a mechanism similar to that observed for non-conjugated polysaccharides seems unlikely in view of the characteristics of the CS immune response, mainly the induction of CD4 + T cell [16,21,49] and CS-specific memory B-cell responses [49]. In addition, similar anti-CS antibody kinetics were previously observed with a delayed third vaccine dose when RTS, S/AS01 was given according to a 0,1,7-month schedule in a phase II study [19]. Recent data from that study however suggest that increases in antibody concentrations and avidity following successive vaccinations are associated with a riskreduction for malaria [50].…”

“…Several other malaria case definitions were used in the phase II and III trials with varying parasite density thresholds, but without major impact on VE estimates, suggesting that any case definition with positive parasitemia is sufficiently specific to avoid biased estimates of VE [15,19,20]. This might be explained by the mechanism of action of the vaccine, which is preerythrocytic and limits infection by preventing the release of merozoites from the liver, but does not alter disease progression and parasite density once blood-stage infection is established.…”

Safety and efficacy of the RTS,S/AS01 E candidate malaria vaccine given with expanded-programme-on-immunisation vaccines: 19 month follow-up of a randomised, open-label, phase 2 trial

“…The vaccine has been assessed with two diff erent proprietary adjuvant systems, AS02 and AS01, both having shown a promising safety profi le in children [5][6][7][8][9] and infants. [10][11][12] The RTS,S antigen includes a carboxy-terminal segment of the Plasmodium falciparum circumsporozoite protein fused to the HBsAg. Simultaneously expressed in yeast cells together with free HBsAg, these antigens assemble into particulate structures.…”

“…A phase 2 trial 12 in Gabon, Ghana, and Tanzania in infants aged 6-10 weeks at fi rst vaccination was done to assess safety, immunogenicity, and effi cacy of two RTS,S/AS01 E schedules (0, 1, 2 month and 0, 1, 7 month schedules) for potential integration into the EPI. Malaria transmission is intense and perennial in these regions, 9,[13][14][15] although the burden of malaria has recently decreased in Lambaréné, Gabon.…”

First Results of Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Children

“…[5][6][7][8][9][10] The vaccine had an acceptable side-effect profile and was immunogenic in children who were 6 weeks of age or older. In addition, the vaccine could be administered safely with other childhood vaccines 8,11 and provided protection against severe malaria. 5 Here, we report the initial results of an ongoing phase 3 trial being conducted at 11 centers in 7 African countries ( Fig.…”