title: The NTS-DBL2X region of VAR2CSA induces cross-reactive antibodies that inhibit adhesion of several Plasmodium falciparum isolates to chondroitin sulfate A.
abstract: BACKGROUND
  Binding to chondroitin sulfate A by VAR2CSA, a parasite protein expressed on infected erythrocytes, allows placental sequestration of Plasmodium falciparum-infected erythrocytes. This leads to severe consequences such as maternal anemia, stillbirths, and intrauterine growth retardation. The latter has been clearly associated to increased morbidity and mortality of the infants. Acquired anti-VAR2CSA antibodies have been associated with improved pregnancy outcomes, suggesting a vaccine could prevent the syndrome. However, identifying functionally important regions in the large VAR2CSA protein is difficult.
  
  
  METHODS
  Using genetic immunization, we raised polyclonal antisera against overlapping segments of VAR2CSA in mice and rabbits. The adhesion-inhibition capacities of induced antisera and of specific antibodies purified from plasma of malaria-exposed pregnant women were assessed on laboratory-adapted parasite lines and field isolates expressing VAR2CSA. Competition enzyme-linked immunosorbent assay (ELISA) was employed to analyze functional resemblance between antibodies induced in animals and those naturally acquired by immune multigravidae.
  
  
  RESULTS
  Antibodies targeting the N-terminal sequence (NTS) up to DBL2X (NTS-DBL2X) efficiently blocked parasite adhesion to chondroitin sulfate A in a manner similar to that of antibodies raised against the entire VAR2CSA extracellular domain. Interestingly, naturally acquired antibodies and those induced by vaccination against NTS-DBL2X target overlapping strain-transcendent anti-adhesion epitopes.
  
  
  CONCLUSIONS
  This study highlights an important step achieved toward development of a protective vaccine against placental malaria.
authors: Unité de Pharmacologie Chimique et Génétique, Université Paris Descartes, ENSCP Chimie ParisTech, CNRS UMR8151, Inserm U 1022, France.
authors: Pascal
authors: P
authors: Bigey
authors: Sédami
authors: S
authors: Gnidehou
authors: Justin
authors: J
authors: Doritchamou
authors: Mickael
authors: M
authors: Quiviger
authors: Firmine
authors: F
authors: Viwami
authors: Aude
authors: A
authors: Couturier
authors: Ali
authors: A
authors: Salanti
authors: Morten A
authors: MA
authors: Nielsen
authors: Daniel
authors: D
authors: Scherman
authors: Philippe
authors: P
authors: Deloron
authors: Nicaise
authors: N
authors: Tuikue Ndam
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion / Q000276:immunology*; D002809:Chondroitin Sulfates / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007110:Immunity, Active / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology*; D051379:Mice; D010957:Plasmids; D010963:Plasmodium falciparum / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D011485:Protein Binding; D011817:Rabbits; D014611:Vaccination
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; C512601:VAR2CSA protein, Plasmodium falciparum; D002809:Chondroitin Sulfates