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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
[ClinicalTrials.gov]
.)
Source Information
From the Centre for Geographic Medicine Research (Coast), Kenya Medical Research Institute, Kilifi, Kenya (P.B., A.O., T.L., P.N., K.O.A., N.M., K.M.); the Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom (P.B., K.M.); the National Institute for Medical Research, Tanga Centre (J.L., S.M., A.M., O.A., S.G., M.M.L.), and the Joint Malaria Programme, Korogwe (J.L., S.M., J.G., A.M., O.A., S.G., C.J.D., E.M.R., M.M.L., L.S.) — both in Tanzania; Centre for Medical Parasitology, University of Copenhagen, Denmark (J.L.); GlaxoSmithKline Biologicals, Rixensart, Belgium (A.L., M.L., J.V., M.-C.D., M.-A.D., J.-F.S., W.R.B., J.C.); the London School of Hygiene and Tropical Medicine, London (J.G., C.J.D., E.M.R., L.S.); Program for Appropriate Technology in Health (PATH) Malaria Vaccine Initiative, Bethesda, MD (P.V., T.C., B.S., T.V.); the International Vaccine Institute, Seoul, Korea (L.S.); and the Mahidol Oxford Research Unit, Bangkok, Thailand (L.S.).
This article (10.1056/NEJMoa0807381) was published at www.nejm.org on December 8, 2008.
Address reprint requests to Dr. Bejon at KEMRI, P.O. Box 230, Mombasa, Kenya, or at pbejon{at}kilifi.kemri-wellcome.org.
Related Letters:
RTS,S/AS01E Vaccine against Malaria
Gosling R. D., Chandramohan D., Bejon P., Leach A., von Seidlein L.
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N Engl J Med 2009;
360:1253-1254, Mar 19, 2009.
Correspondence
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