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  • Title: Induction of cross-reactive immune responses to NTS-DBL-1alpha/x of PfEMP1 and in vivo protection on challenge with Plasmodium falciparum.
    Author: Ahuja S, Pettersson F, Moll K, Jonsson C, Wahlgren M, Chen Q.
    Journal: Vaccine; 2006 Aug 28; 24(35-36):6140-54. PubMed ID: 16837110.
    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.
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