Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age

Philip Bejon, John Lusingu, Ally Olotu, Amanda Leach, Marc Lievens, Johan Vekemans, Salum Mshamu, Trudie Lang, Jayne Gould, Marie Claude Dubois, Marie Ange Demoitié, Jean Francois Stallaert, Preeti Vansadia, Terrell Carter, Patricia Njuguna, Ken O. Awuondo, Anangisye Malabeja, Omar Abdul, Samwel Gesase, Neema MturiChris J. Drakeley, Barbara Savarese, Tonya Villafana, W. Ripley Ballou, Joe Cohen, Eleanor M. Riley, Martha M. Lemnge, Kevin Marsh, Lorenz Von Seidlein

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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.)

    Original languageEnglish
    Pages (from-to)2521-2532
    Number of pages12
    JournalNew England Journal of Medicine
    Volume359
    Issue number24
    DOIs
    Publication statusPublished - 2008

    Fingerprint

    Dive into the research topics of 'Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age'. Together they form a unique fingerprint.

    Cite this