Abstract
Objective:The objective was to measure the efficacy of the vaccination regimen FFM ME-TRAP in preventing episodes of clinical malaria among children in a malaria endemic area. FFM ME-TRAP is sequential immunisation with two attenuated poxvirus vectors (FP9 and modified vaccinia virus Ankara), which both deliver the pre-erythrocytic malaria antigen construct multiple epitope–thrombospondin-related adhesion protein (ME-TRAP).Design:The trial was randomised and double-blinded.Setting:The setting was a rural, malaria-endemic area of coastal Kenya.Participants:We vaccinated 405 healthy 1- to 6-year-old children.Interventions:Participants were randomised to vaccination with either FFM ME-TRAP or control (rabies vaccine).Outcome Measures:Following antimalarial drug treatment children were seen weekly and whenever they were unwell during nine months of monitoring. The axillary temperature was measured, and blood films taken when febrile. The primary analysis was time to a parasitaemia of over 2,500 parasites/μl.Results:The regime was moderately immunogenic, but the magnitude of T cell responses was lower than in previous studies. In intention to treat (ITT) analysis, time to first episode was shorter in the FFM ME-TRAP group. The cumulative incidence of febrile malaria was 52/190 (27%) for FFM ME-TRAP and 40/197 (20%) among controls (hazard ratio = 1.52). This was not statistically significant (95% confidence interval [CI] 1.0–2.3; p = 0.14 by log-rank). A group of 346 children were vaccinated according to protocol (ATP). Among these children, the hazard ratio was 1.3 (95% CI 0.8–2.1; p = 0.55 by log-rank). When multiple malaria episodes were included in the analyses, the incidence rate ratios were 1.6 (95% CI 1.1–2.3); p = 0.017 for ITT, and 1.4 (95% CI 0.9–2.1); p = 0.16 for ATP. Haemoglobin and parasitaemia in cross-sectional surveys at 3 and 9 mo did not differ by treatment group. Among children vaccinated with FFM ME-TRAP, there was no correlation between immunogenicity and malaria incidence.Conclusions:No protection was induced against febrile malaria by this vaccine regimen. Future field studies will require vaccinations with stronger immunogenicity in children living in malarious areas.
Highlights
More than 1 million people die each year from malaria, and this number is likely to increase [1]
Prime-boost vaccination with FP9 with modified vaccinia virus Ankara (MVA), both recombinant for the pre-erythrocytic antigen construct was safe, immunogenic, and partially protective in malaria-naıve adults exposed to experimental challenge [8]
FFM multiple epitope (ME)-TRAP was safe when given to 1- to 6-year-old children in a malaria-endemic area
Summary
More than 1 million people die each year from malaria, and this number is likely to increase [1]. There is evidence that T cells are protective against malaria in animal models [2], field studies [3], and following immunization with irradiated sporozoites [4] This evidence has prompted the development of a heterologous primeboost strategy to induce T cell responses against preerythrocytic stages of parasite development [5]. This approach (termed ‘‘prime-boost’’) uses two different delivery methods to transmit the same antigen (part of a protein from the malaria parasite that can trigger an immune response). Previous studies done in adult UK volunteers have been promising, achieving an immune response and some protection against malaria when volunteers were deliberately infected This approach has not been tested in the group most in need of a vaccine—young African children. The children were followed up for nine months, and the primary aim of the trial was to compare the occurrence of clinical malaria (fever combined with malaria parasites in the blood) in the two groups
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