A Phase 2b Randomised Trial of the Candidate Malaria Vaccines FP9 ME-TRAP and MVA ME-TRAP among Children in Kenya
Date
2006Author
Bejon, Philip
Mwacharo, Jedidah
Kai, Oscar
Tabitha, Mwangi
Milligan, Paul
Todryk, Stephen
Keating, Sheila
Lang, Trudie
Lowe, Brett
Gikonyo, Caroline
Molyneux, Catherine
Fegan, Greg
Gilbert, Sarah C.
Peshu, Norbert
Marsh, Kevin
Hill, Adrian V. S.
Metadata
Show full item recordAbstract
Objective: The objective was to measure the efficacy of the vaccination regimen FFM METRAP
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/ll.
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 ¼ 1.52). This was not
statistically significant (95% confidence interval [CI] 1.0–2.3; p ¼ 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 ¼ 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 ¼ 0.017 for ITT,
and 1.4 (95% CI 0.9–2.1); p ¼ 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