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

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)-gamma3 domain of the P. falciparum erythrocyte membrane protein 1 (PfEMP1(CSA)) (DBL-gamma3(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-gamma3(CSA) (rDBL-gamma3(CSA)) in insect cells, corresponding to 2 variant DBL-gamma3(CSA) subtypes that mediate binding to CSA in laboratory lines and placental isolates. Both recombinant cysteine-rich DBL-gamma3(CSA) domains blocked IEs(CSA) binding to CSA. Immunization of mice, with the rDBL-gamma3(CSA)-FCR3 and rDBL-gamma3(CSA)-3D7 domains, resulted in the generation of antibodies recognizing homologous and heterologous rDBL-gamma3(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-gamma3(CSA) is the target of inhibitory and pan-reactive antibodies. Saimiri sciureus monkeys immunized with FCR3-rDBL-gamma3(CSA) developed pan-reactive and inhibitory antibodies, a finding suggesting that the development of a vaccine to prevent maternal malaria is feasible.
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https://hal.umontpellier.fr/hal-02507379
Contributeur : Nathalie Salvy-Cordoba <>
Soumis le : vendredi 13 mars 2020 - 10:12:46
Dernière modification le : jeudi 19 mars 2020 - 01:14:18

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Fabio t. m. Costa, Thierry Fusai, Daniel Parzy, Yvon Sterkers, Marylin Torrentino, et al.. Immunization with Recombinant Duffy Binding–Like–γ3 Induces Pan‐Reactive and Adhesion‐Blocking Antibodies against Placental Chondroitin Sulfate A–Binding Plasmodium falciparum Parasites. Journal of Infectious Diseases, Oxford University Press (OUP), 2003, 188 (1), pp.153-164. ⟨10.1086/375800⟩. ⟨hal-02507379⟩

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