title: Induction of cross-reactive immune responses to NTS-DBL-1alpha/x of PfEMP1 and in vivo protection on challenge with Plasmodium falciparum.
abstract: 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-1alpha/x fusion domains from the 3D7 genome parasite emulsified in Montanide ISA 720. Cross-reactivity was elicited to these diverse DBL-1alpha/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-1alpha/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.
authors.affiliation: Microbiology and Tumor Biology Center (MTC), Karolinska Institute, P.O. Box 280, SE-17177 Stockholm, Sweden.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Ahuja
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pettersson
authors.forename: Kirsten
authors.initials: K
authors.lastname: Moll
authors.forename: Cathrine
authors.initials: C
authors.lastname: Jonsson
authors.forename: Mats
authors.initials: M
authors.lastname: Wahlgren
authors.forename: Qijun
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000818:Animals; D000917:Antibody Formation; D003001:Cloning, Molecular; D003429:Cross Reactions / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D005982:Glutathione Transferase; D007114:Immunization; D015151:Immunoblotting; D016778:Malaria, Falciparum / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D005982:Glutathione Transferase