Effect of the Pre-erythrocytic candidate malaria vaccine RTS,S/AS01e on blood stage immunity in young children.

Phillip Bejon, Jackie Cook, Elke Bergmann-Leitner, Ally Olotu, John Lusingu, Jedidah Mwacharo, Johan Vekemans, Patricia Njuguna, Amanda Leach, Marc Lievens, Sheetij Dutta, Lorenz Von Seidlein, Barbara Savarese, Tonya Villafana, Martha Lemnge, Joe Cohen, Kevin Marsh, Patrick Corran, Evelina Angov, Eleanor RileyChris Drakeley

    Research output: Contribution to journalArticle

    Abstract

    Background: RTS,S/AS01E is the lead candidate malaria vaccine and confers pre-erythrocytic immunity. Vaccination may therefore impact acquired immunity to blood-stage malaria parasites after natural infection.

    Methods: We measured, by enzyme-linked immunosorbent assay, antibodies to 4 Plasmodium falciparum merozoite antigens (AMA-1, MSP-142, EBA-175, and MSP-3) and by growth inhibitory activity (GIA) using 2 parasite clones (FV0 and 3D7) at 4 times on 860 children who were randomized to receive with RTS,S/AS01 E or a control vaccine.

    Results: Antibody concentrations to AMA-1, EBA-175, and MSP-142 decreased with age during the first year of life, then increased to 32 months of age. Anti - MSP-3 antibody concentrations gradually increased, and GIA gradually decreased up to 32 months. Vaccination with RTS,S/AS01E resulted in modest reductions in AMA-1, EBA-175, MSP-142, and MSP-3 antibody concentrations and no significant change in GIA. Increasing anti-merozoite antibody concentrations and GIA were prospectively associated with increased risk of clinical malaria.

    Conclusions: Vaccination with RTS,S/AS01E reduces exposure to blood-stage parasites and, thus, reduces antimerozoite antigen antibody concentrations. However, in this study, these antibodies were not correlates of clinical immunity to malaria. Instead, heterogeneous exposure led to confounded, positive associations between increasing antibody concentration and increasing risk of clinical malaria.

    Original languageEnglish
    Pages (from-to)9-18
    Number of pages10
    JournalJournal of Infectious Diseases
    Volume204
    Issue number1
    DOIs
    Publication statusPublished - 1 Jul 2011

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