title: Avidity of anti-circumsporozoite antibodies following vaccination with RTS,S/AS01E in young children.
abstract: BACKGROUND
  The nature of protective immune responses elicited by immunization with the candidate malaria vaccine RTS,S is still incompletely understood. Antibody levels correlate with protection against malaria infection, but considerable variation in outcome is unexplained (e.g., children may experience malaria despite high anti-circumsporozoite [CS] titers).
  
  
  RESULTS
  We measured the avidity index (AI) of the anti-CS antibodies raised in subgroup of 5-17 month old children in Kenya who were vaccinated with three doses of RTS,S/AS01E between March and August 2007. We evaluated the association between the AI and the subsequent risk of clinical malaria. We selected 19 cases (i.e., with clinical malaria) and 42 controls (i.e., without clinical malaria), matching for anti-CS antibody levels and malaria exposure. We assessed their sera collected 1 month after the third dose of the vaccine, in March 2008 (range 4-10 months after the third vaccine), and at 12 months after the third vaccine dose. The mean AI was 45.2 (95% CI: 42.4 to 48.1), 45.3 (95% CI: 41.4 to 49.1) and 46.2 (95% CI; 43.2 to 49.3) at 1 month, in March 2008 (4-10 months), and at 12 months after the third vaccination, respectively (p = 0.9 by ANOVA test for variation over time). The AI was not associated with protection from clinical malaria (OR = 0.90; 95% CI: 0.49 to 1.66; p = 0.74). The AI was higher in children with high malaria exposure, as measured using the weighted local prevalence of malaria, compared to those with low malaria exposure at 1 month post dose 3 (p = 0.035).
  
  
  CONCLUSIONS
  Our data suggest that in RTS,S/AS01E-vaccinated children residing in malaria endemic countries, the avidity of anti-circumsporozoite antibodies, as measured using an elution ELISA method, was not associated with protection from clinical malaria. Prior natural malaria exposure might have primed the response to RTS,S/AS01E vaccination.
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research, Coast, Kilifi, Kenya; Ifakara Health Institute, Bagamoyo, Tanzania.
authors.forename: Ally
authors.initials: A
authors.lastname: Olotu
authors.affiliation: Centre for Vaccinology, Ghent University, Ghent, Belgium.
authors.forename: Frederic
authors.initials: F
authors.lastname: Clement
authors.affiliation: GlaxoSmithKline Vaccines, Wavre, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: Jongert
authors.affiliation: GlaxoSmithKline Vaccines, Wavre, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Vekemans
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research, Coast, Kilifi, Kenya.
authors.forename: Patricia
authors.initials: P
authors.lastname: Njuguna
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research, Coast, Kilifi, Kenya.
authors.forename: Francis M
authors.initials: FM
authors.lastname: Ndungu
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research, Coast, Kilifi, Kenya.
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.affiliation: Centre for Vaccinology, Ghent University, Ghent, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research, Coast, Kilifi, Kenya.
authors.forename: Philip
authors.initials: P
authors.lastname: Bejon
mesh_terms: D000913:Antibodies, Protozoan / Q000097:blood* / Q000276:immunology; D000915:Antibody Affinity; D016022:Case-Control Studies; D006801:Humans; D007223:Infant; D007630:Kenya; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D015800:Protozoan Proteins / Q000276:immunology*; D012306:Risk
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C533816:RTS,S-AS01E vaccine; C041595:circumsporozoite protein, Protozoan