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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Epitope mapping and topographic analysis of VAR2CSA DBL3X involved in P. falciparum placental sequestration
PLoS Pathogens, Volume 2, No. 11, Year 2006
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Description
Pregnancy-associated malaria is a major health problem, which mainly affects primigravidae living in malaria endemic areas. The syndrome is precipitated by accumulation of infected erythrocytes in placental tissue through an interaction between chondroitin sulphate A on syncytiotrophoblasts and a parasite-encoded protein on the surface of infected erythrocytes, believed to be VAR2CSA. VAR2CSA is a polymorphic protein of approximately 3,000 amino acids forming six Duffy-binding-like (DBL) domains. For vaccine development it is important to define the antigenic targets for protective antibodies and to characterize the consequences of sequence variation. In this study, we used a combination of in silico tools, peptide arrays, and structural modeling to show that sequence variation mainly occurs in regions under strong diversifying selection, predicted to form flexible loops. These regions are the main targets of naturally acquired immunoglobulin gamma and accessible for antibodies reacting with native VAR2CSA on infected erythrocytes. Interestingly, surface reactive anti-VAR2CSA antibodies also target a conserved DBL3X region predicted to form an α-helix. Finally, we could identify DBL3X sequence motifs that were more likely to occur in parasites isolated from primi- and multigravidae, respectively. These findings strengthen the vaccine candidacy of VAR2CSA and will be important for choosing epitopes and variants of DBL3X to be included in a vaccine protecting women against pregnancy-associated malaria. © 2006 Dahlbäck et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC1636682/bin/ppat.0020124.sg001.ppt
https://efashare.b-cdn.net/share/pmc/articles/PMC1636682/bin/ppat.0020124.sg002.ppt
Authors & Co-Authors
Dahlbäck, Madeleine A.
Denmark, Copenhagen
Rigshospitalet
Rask, Thomas S.
Denmark, Lyngby
Technical University of Denmark
Andersen, Pernille Haste
Denmark, Lyngby
Technical University of Denmark
Nielsen, M. A.
Denmark, Copenhagen
Rigshospitalet
Tuikue-Ndam, Nicaise
Denmark, Copenhagen
Rigshospitalet
France, Marseille
Ird Institut de Recherche Pour le Developpement
Resende, Mafalda
Denmark, Copenhagen
Rigshospitalet
Turner, Louise
Denmark, Copenhagen
Rigshospitalet
Deloron, Philippe
France, Marseille
Ird Institut de Recherche Pour le Developpement
Hviid, Lars
Denmark, Copenhagen
Rigshospitalet
Lund, Ole Sogaard
Denmark, Lyngby
Technical University of Denmark
Pedersen, Anders Gorm
Denmark, Lyngby
Technical University of Denmark
G. Theander, Thor Grundtvig
Denmark, Copenhagen
Rigshospitalet
Salanti, Ali
Denmark, Copenhagen
Rigshospitalet
Statistics
Citations: 78
Authors: 13
Affiliations: 3
Identifiers
Doi:
10.1371/journal.ppat.0020124
ISSN:
15537374
Research Areas
Infectious Diseases
Maternal And Child Health
Sexual And Reproductive Health
Participants Gender
Female