Induction of cross-reactive immune responses to NTS-DBL-1α/x of PfEMP1 and in vivo protection on challenge with Plasmodium falciparum

The interactions of Plasmodium falciparum infected erythrocytes parasitized red blood cells (pRBC) with endothelial receptors and erythrocytes are mediated by multiple Duffy-binding like (DBL) and cysteine-rich interdomain region (CIDR) domains harboured in the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). The success of a subunit vaccine based on PfEMP1 depends on its ability to elicit cross-reactive responses to a substantial number of PfEMP1 variants. We have here evaluated serological PfEMP1 cross-reactivity by immunizing rats with phylogenetically diverse recombinant NTS-DBL-1α/x fusion domains from the 3D7 genome parasite emulsified in Montanide ISA 720. Cross-reactivity was elicited to these diverse DBL-1α/x domains as measured by ELISA and by immunoblotting. Employing a novel in vivo model of human infected erythrocyte sequestration, immunized animals were challenged with the FCR3S1.2 clone and cross-protection in terms of reduction in lung sequestration amounting to approximately 50% was demonstrated. Our results suggest that immunization with phylogenetically distant DBL-1α/x variants, can elicit partial cross-protection to challenge with the parasites harbouring a distant variant. These observations have implications for the design of multi-component vaccines against P. falciparum malaria.