A phase 2b randomised trial of the candidate malaria vaccines FP9 ME-TRAP and MVA ME-TRAP among children in Kenya.
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).


METHODS
The trial was randomised and double-blinded.


METHODS
The setting was a rural, malaria-endemic area of coastal Kenya.


METHODS
We vaccinated 405 healthy 1- to 6-year-old children.


METHODS
Participants were randomised to vaccination with either FFM ME-TRAP or control (rabies vaccine).


METHODS
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/mul.


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.
Bejon
Philip
P
Kenya Medical Research Institute, Centre for Geographical Medicine Research (Coast), Kilifi, Kenya. pbejon@well.ox.ac.uk
Mwacharo
Jedidah
J
Kai
Oscar
O
Mwangi
Tabitha
T
Milligan
Paul
P
Todryk
Stephen
S
Keating
Sheila
S
Lang
Trudie
T
Lowe
Brett
B
Gikonyo
Caroline
C
Molyneux
Catherine
C
Fegan
Greg
G
Gilbert
Sarah C
SC
Peshu
Norbert
N
Marsh
Kevin
K
Hill
Adrian V S
AV