RTS,S/AS01E: Blood Stage Immunity in Young Children

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Journal of Infectious Diseases
Volume 204 Issue 1   July 1, 2011
http://www.journals.uchicago.edu/toc/jid/current

MAJOR ARTICLES AND BRIEF REPORTS: PARASITES
Philip 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 M. Lemnge, Joe Cohen, Kevin Marsh, Patrick H. Corran, Evelina Angov, Eleanor M. Riley, and Chris J. Drakeley

Effect of the Pre-erythrocytic Candidate Malaria Vaccine RTS,S/AS01E on Blood Stage Immunity in Young Children
J Infect Dis. (2011) 204(1): 9-18 doi:10.1093/infdis/jir222

Abstract [Free full text]
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/AS01E or a control vaccine.

Results. Antibody concentrations to AMA-1, EBA-175, and MSP-1 42 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 anti-merozoite 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.