Identification of a Major Dimorphic Region in the Functionally Critical N-Terminal ID1 Domain of VAR2CSA |
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| Authors: | Justin Doritchamou Audrey Sabbagh Jakob S Jespersen Emmanuelle Renard Ali Salanti Morten A Nielsen Philippe Deloron Nicaise Tuikue Ndam |
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| Institution: | 1. PRES Sorbonne Paris Cité, Université Paris Descartes, Paris, France.; 2. UMR216 - MERIT, Institut de Recherche pour le Développement, Paris, France.; 3. Centre for Medical Parasitology, University of Copenhagen, Copenhagen, Denmark.; Bernhard Nocht Institute for Tropical Medicine, GERMANY, |
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| Abstract: | The VAR2CSA protein of Plasmodium falciparum is transported to and expressed on the infected erythrocyte surface where it plays a key role in placental malaria (PM). It is the current leading candidate for a vaccine to prevent PM. However, the antigenic polymorphism integral to VAR2CSA poses a challenge for vaccine development. Based on detailed analysis of polymorphisms in the sequence of its ligand-binding N-terminal region, currently the main focus for vaccine development, we assessed var2csa from parasite isolates infecting pregnant women. The results reveal for the first time the presence of a major dimorphic region in the functionally critical N-terminal ID1 domain. Parasite isolates expressing VAR2CSA with particular motifs present within this domain are associated with gravidity- and parasite density-related effects. These observations are of particular interest in guiding efforts with respect to optimization of the VAR2CSA-based vaccines currently under development. |
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