Relationship between sequence polymorphism and antibody cross-reactivity between AMA1 alleles. Panels A-K show the relationship between the level of antibody cross-reactivity between AMA1 alleles measured by competition ELISA and the number of amino acid differences between the AMA1 alleles across Domains I, II and III. Each panel represents the relationship between a single AMA1 allele to the other 10 AMA1 alleles tested. For example: Panel A shows the degree of cross-reactivity that antibodies to 10 other AMA1 alleles have to 3D7 AMA1 by ELISA and the degree of amino acid similarity which each of the 10 alleles have to 3D7 AMA1. Significant negative correlations were seen between cross-reactivity and number of sequence differences for antibodies to 7G8 (Spearman’s ρ (rho) = -0.822, P = 0.0047) and XIE (ρ = -0.652, P = 0.0438). Negative correlations of borderline statistical significance were observed for antibodies to W2mef (ρ = -0.609, P = 0.0667), FVO (ρ = -0.583, P = 0.0806) and 2006 (ρ = -0.587, P = 0.0806). No significant correlations were observed for any other alleles. Data on antibody cross-reactivity were obtained from testing PNG children.