Acquisition of Functional Antibodies That Block the Binding of Erythrocyte-Binding Antigen 175 and Protection Against Plasmodium falciparum Malaria in XXXX .

@entity1 @entity311 @entity3138
BACKGROUND:    The targets and mechanisms of @entity1 immunity to @entity311 are poorly understood, which poses a major barrier to @entity311 vaccine development. Antibodies play a key role in @entity1 immunity and may act by inhibiting receptor-binding functions of key merozoite invasion ligands. Antibodies to the major invasion ligand and vaccine candidate, erythrocyte-binding antigen 175 (EBA-175), have been linked with protection, but how these antibodies function has not been established. METHODS:    We developed 2 new assays that quantify the ability of antibodies to inhibit binding of EBA-175 to its @entity3138 , glycophorin A, using either native or recombinant EBA-175. Binding-inhibitory antibodies were evaluated in a longitudinal cohort study of Papua New Guinean @entity1 and related to risk of @entity311 , age, infection status, and markers of parasite exposure. RESULTS:    Binding-inhibition assays (BIAs) were reproducible, and the 2 assays had a high level of agreement. Inhibitory antibodies were common among @entity1 , acquired in association with markers of increasing parasite exposure, and high in those @entity1 with active infection. Inhibitory antibodies correlated with total immunoglobulin G levels to the EBA-175 binding domain (region II). Importantly, binding-inhibitory antibodies were significantly associated with protection from symptomatic @entity311 when measured using either BIA. CONCLUSIONS:    Findings suggest that naturally acquired binding-inhibitory antibodies are an important functional mechanism that contributes to protection against @entity311 and further supports the potential of EBA-175 as a vaccine candidate. Identifying vaccines and approaches that induce potent binding-inhibitory antibodies may be a valuable strategy in the development of highly efficacious @entity311 vaccines.
