Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age.
BACKGROUND
Plasmodium falciparum malaria is a pressing global health problem. A previous study of the malaria vaccine RTS,S (which targets the circumsporozoite protein), given with an adjuvant system (AS02A), showed a 30% rate of protection against clinical malaria in children 1 to 4 years of age. We evaluated the efficacy of RTS,S given with a more immunogenic adjuvant system (AS01E) in children 5 to 17 months of age, a target population for vaccine licensure.


METHODS
We conducted a double-blind, randomized trial of RTS,S/AS01E vaccine as compared with rabies vaccine in children in Kilifi, Kenya, and Korogwe, Tanzania. The primary end point was fever with a falciparum parasitemia density of more than 2500 parasites per microliter, and the mean duration of follow-up was 7.9 months (range, 4.5 to 10.5).


RESULTS
A total of 894 children were randomly assigned to receive the RTS,S/AS01E vaccine or the control (rabies) vaccine. Among the 809 children who completed the study procedures according to the protocol, the cumulative number in whom clinical malaria developed was 32 of 402 assigned to receive RTS,S/AS01E and 66 of 407 assigned to receive the rabies vaccine; the adjusted efficacy rate for RTS,S/AS01E was 53% (95% confidence interval [CI], 28 to 69; P<0.001) on the basis of Cox regression. Overall, there were 38 episodes of clinical malaria among recipients of RTS,S/AS01E, as compared with 86 episodes among recipients of the rabies vaccine, with an adjusted rate of efficacy against all malarial episodes of 56% (95% CI, 31 to 72; P<0.001). All 894 children were included in the intention-to-treat analysis, which showed an unadjusted efficacy rate of 49% (95% CI, 26 to 65; P<0.001). There were fewer serious adverse events among recipients of RTS,S/AS01E, and this reduction was not only due to a difference in the number of admissions directly attributable to malaria.


CONCLUSIONS
RTS,S/AS01E shows promise as a candidate malaria vaccine. (ClinicalTrials.gov number, NCT00380393.)
Bejon
Philip
P
Centre for Geographic Medicine Research (Coast), Kenya Medical Research Institute, Kilifi, Kenya. pbejon@kilifi.kemri-wellcome.org
Lusingu
John
J
Olotu
Ally
A
Leach
Amanda
A
Lievens
Marc
M
Vekemans
Johan
J
Mshamu
Salum
S
Lang
Trudie
T
Gould
Jayne
J
Dubois
Marie-Claude
MC
Demoitié
Marie-Ange
MA
Stallaert
Jean-Francois
JF
Vansadia
Preeti
P
Carter
Terrell
T
Njuguna
Patricia
P
Awuondo
Ken O
KO
Malabeja
Anangisye
A
Abdul
Omar
O
Gesase
Samwel
S
Mturi
Neema
N
Drakeley
Chris J
CJ
Savarese
Barbara
B
Villafana
Tonya
T
Ballou
W Ripley
WR
Cohen
Joe
J
Riley
Eleanor M
EM
Lemnge
Martha M
MM
Marsh
Kevin
K
von Seidlein
Lorenz
L
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology; D016016:Proportional Hazards Models; D015800:Protozoan Proteins / Q000276:immunology
D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C533816:RTS,S-AS01E vaccine; C041595:circumsporozoite protein, Protozoan