title: Effect of the pre-erythrocytic candidate malaria vaccine RTS,S/AS01E on blood stage immunity in young children.
abstract: RTS,S/AS01(E) 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.
  
  
  
  We measured, by enzyme-linked immunosorbent assay, antibodies to 4 Plasmodium falciparum merozoite antigens (AMA-1, MSP-1(42), 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.
  
  
  
  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/AS01(E) resulted in modest reductions in AMA-1, EBA-175, MSP-1(42), 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.
  
  
  
  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.
authors.affiliation: Kenya Medical Research Institute, Centre for Geographic Medicine Research, Kilifi, Kenya. pbejon@kilifi.kemri-wellcome.org
authors.forename: Philip
authors.initials: P
authors.lastname: Bejon
authors.forename: Jackie
authors.initials: J
authors.lastname: Cook
authors.forename: Elke
authors.initials: E
authors.lastname: Bergmann-Leitner
authors.forename: Ally
authors.initials: A
authors.lastname: Olotu
authors.forename: John
authors.initials: J
authors.lastname: Lusingu
authors.forename: Jedidah
authors.initials: J
authors.lastname: Mwacharo
authors.forename: Johan
authors.initials: J
authors.lastname: Vekemans
authors.forename: Patricia
authors.initials: P
authors.lastname: Njuguna
authors.forename: Amanda
authors.initials: A
authors.lastname: Leach
authors.forename: Marc
authors.initials: M
authors.lastname: Lievens
authors.forename: Sheetij
authors.initials: S
authors.lastname: Dutta
authors.forename: Lorenz
authors.initials: L
authors.lastname: von Seidlein
authors.forename: Barbara
authors.initials: B
authors.lastname: Savarese
authors.forename: Tonya
authors.initials: T
authors.lastname: Villafana
authors.forename: Martha M
authors.initials: MM
authors.lastname: Lemnge
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Corran
authors.forename: Evelina
authors.initials: E
authors.lastname: Angov
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Riley
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Drakeley
mesh_terms: D000913:Antibodies, Protozoan / Q000097:blood*; D002675:Child, Preschool; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies / Q000379:methods; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000276:immunology*; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology; D012307:Risk Factors
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C533816:RTS,S-AS01E vaccine