Immunogenicity of the Plasmodium falciparum PfEMP1-VarO Adhesin: Induction of Surface-Reactive and Rosette-Disrupting Antibodies to VarO Infected Erythrocytes.

摘要: Adhesion of Plasmodium falciparum-infected red blood cells (iRBC) to human erythrocytes (i.e. rosetting) is associated with severe malaria. Rosetting results from interactions between a subset variant PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1) adhesins and specific receptors. Interfering such considered promising intervention against To evaluate the feasibility vaccine strategy targetting rosetting, we have used here Palo Alto 89F5 VarO rosetting model. PfEMP1-VarO consists five Duffy-Binding Like domains (DBL1-5) one Cysteine-rich Interdomain Region (CIDR1). The binding domain has been mapped DBL1 ABO group was identified as receptor. Here, study immunogenicity all six recombinant DBL1- CIDR1 Head in BALB/c outbred OF1 mice. Five readouts antibody responses are explored: ELISA titres on antigen, VarO-iRBC immunoblot reactivity, surface-reactivity, capacity disrupt rosettes prevent rosette formation. For three domains, explore influence expression system antigenicity immunogenicity. We show that correctly folded elicit high induce homogeneous response mice after injections. High levels rosette-disrupting rosette-preventing antibodies induced by domain. Reduced-alkylated or denatured proteins fail surface-reacting antibodies, indicating surface epitopes conformational. also report limited cross-reactivity some domains. These highlight individual animals provide strong basis for rational vaccination targeting rosetting.