Immunization with Recombinant Duffy Binding–Like–γ3 Induces Pan‐Reactive and Adhesion‐Blocking Antibodies against Placental Chondroitin Sulfate A–BindingPlasmodium falciparumParasites

Open Access

1 July 2003

journal article
Published by Oxford University Press (OUP) in The Journal of Infectious Diseases

Vol. 188 (1) , 153-164
https://doi.org/10.1086/375800

Abstract

Maternal malaria is associated with the sequestration, in the placenta, of Plasmodium falciparum-infected erythrocytes onto chondroitin sulfate A (CSA), via the duffy binding-like (DBL)-γ3 domain of the P. falciparum erythrocyte membrane protein 1 (PfEMP1^CSA) (DBL-γ3^CSA). The production of antibodies against CSA-binding infected erythrocytes (IEs^CSA) is correlated with resistance to maternal malaria in multiparous women. We produced recombinant DBL-γ3^CSA (rDBL-γ3^CSA) in insect cells, corresponding to 2 variant DBL-γ3^CSA subtypes that mediate binding to CSA in laboratory lines and placental isolates. Both recombinant cysteine-rich DBL-γ3_CSA domains blocked IEs^CSA binding to CSA. Immunization of mice, with the rDBL-γ3^CSA-FCR3 and rDBL-γ3^CSA-3D7 domains, resulted in the generation of antibodies recognizing homologous and heterologous rDBL-γ3^CSA, a finding indicating conserved epitopes inducing a pan-reactive immune response. Mouse monoclonal antibodies (MAbs) against both recombinant proteins were pan-reactive with various IEs^CSA . One MAb efficiently inhibited and reversed IE^CSA cytoadhesion to endothelial cells in vitro. Thus, DBL-γ3^CSA is the target of inhibitory and pan-reactive antibodies. Saimiri sciureus monkeys immunized with FCR3-rDBL-γ3^CSA developed pan-reactive and inhibitory antibodies, a finding suggesting that the development of a vaccine to prevent maternal malaria is feasible.

Keywords

This publication has 0 references indexed in Scilit: