Identification and characterization of B-cell epitopes in the DBL4e domain of VAR2CSA
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Identification and characterization of B-cell epitopes in the DBL4e domain of VAR2CSA. / Ditlev, Sisse B; Nielsen, Morten A; Resende, Mafalda; Agerbæk, Mette Ø; Pinto, Vera V; Andersen, Pernille H; Magistrado, Pamela; Lusingu, John; Dahlbäck, Madeleine; Theander, Thor G; Salanti, Ali.
In: P L o S One, Vol. 7, No. 9, 2012, p. e43663.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Identification and characterization of B-cell epitopes in the DBL4e domain of VAR2CSA
AU - Ditlev, Sisse B
AU - Nielsen, Morten A
AU - Resende, Mafalda
AU - Agerbæk, Mette Ø
AU - Pinto, Vera V
AU - Andersen, Pernille H
AU - Magistrado, Pamela
AU - Lusingu, John
AU - Dahlbäck, Madeleine
AU - Theander, Thor G
AU - Salanti, Ali
PY - 2012
Y1 - 2012
N2 - Malaria during pregnancy in Plasmodium falciparum endemic regions is a major cause of mortality and severe morbidity. VAR2CSA is the parasite ligand responsible for sequestration of Plasmodium falciparum infected erythrocytes to the receptor chondroitin sulfate A (CSA) in the placenta and is the leading candidate for a placental malaria vaccine. Antibodies induced in rats against the recombinant DBL4e domain of VAR2CSA inhibit the binding of a number of laboratory and field parasite isolates to CSA. In this study, we used a DBL4e peptide-array to identify epitopes targeted by DBL4e-specific antibodies that inhibit CSA-binding of infected erythrocytes. We identified three regions of overlapping peptides which were highly antigenic. One peptide region distinguished itself particularly by showing a clear difference in the binding profile of highly parasite blocking IgG compared to the IgG with low capacity to inhibit parasite adhesion to CSA. This region was further characterized and together these results suggest that even though antibodies against the synthetic peptides which cover this region did not recognize native protein, the results using the mutant domain suggest that this linear epitope might be involved in the induction of inhibitory antibodies induced by the recombinant DBL4e domain.
AB - Malaria during pregnancy in Plasmodium falciparum endemic regions is a major cause of mortality and severe morbidity. VAR2CSA is the parasite ligand responsible for sequestration of Plasmodium falciparum infected erythrocytes to the receptor chondroitin sulfate A (CSA) in the placenta and is the leading candidate for a placental malaria vaccine. Antibodies induced in rats against the recombinant DBL4e domain of VAR2CSA inhibit the binding of a number of laboratory and field parasite isolates to CSA. In this study, we used a DBL4e peptide-array to identify epitopes targeted by DBL4e-specific antibodies that inhibit CSA-binding of infected erythrocytes. We identified three regions of overlapping peptides which were highly antigenic. One peptide region distinguished itself particularly by showing a clear difference in the binding profile of highly parasite blocking IgG compared to the IgG with low capacity to inhibit parasite adhesion to CSA. This region was further characterized and together these results suggest that even though antibodies against the synthetic peptides which cover this region did not recognize native protein, the results using the mutant domain suggest that this linear epitope might be involved in the induction of inhibitory antibodies induced by the recombinant DBL4e domain.
U2 - 10.1371/journal.pone.0043663
DO - 10.1371/journal.pone.0043663
M3 - Journal article
C2 - 22970138
VL - 7
SP - e43663
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 9
ER -
ID: 41913437