title: Identification of a Major Dimorphic Region in the Functionally Critical N-Terminal ID1 Domain of VAR2CSA.
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.
authors.affiliation: PRES Sorbonne Paris Cité, Université Paris Descartes, Paris, France; UMR216 - MERIT, Institut de Recherche pour le Développement, Paris, France.
authors.forename: Justin
authors.initials: J
authors.lastname: Doritchamou
authors.affiliation: PRES Sorbonne Paris Cité, Université Paris Descartes, Paris, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Sabbagh
authors.affiliation: Centre for Medical Parasitology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jakob S
authors.initials: JS
authors.lastname: Jespersen
authors.affiliation: PRES Sorbonne Paris Cité, Université Paris Descartes, Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Renard
authors.affiliation: Centre for Medical Parasitology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ali
authors.initials: A
authors.lastname: Salanti
authors.affiliation: Centre for Medical Parasitology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Morten A
authors.initials: MA
authors.lastname: Nielsen
authors.affiliation: PRES Sorbonne Paris Cité, Université Paris Descartes, Paris, France; UMR216 - MERIT, Institut de Recherche pour le Développement, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Deloron
authors.affiliation: PRES Sorbonne Paris Cité, Université Paris Descartes, Paris, France; UMR216 - MERIT, Institut de Recherche pour le Développement, Paris, France.
authors.forename: Nicaise
authors.initials: N
authors.lastname: Tuikue Ndam
mesh_terms: D000953:Antigens, Protozoan / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D005865:Gestational Age; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011247:Pregnancy; D017434:Protein Structure, Tertiary; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; C512601:VAR2CSA protein, Plasmodium falciparum; D014614:Vaccines, Synthetic