Differential adhesion-inhibitory patterns of antibodies raised against two major variants of the NTS-DBL2X region of VAR2CSA.
Vaccine
; 31(41): 4516-22, 2013 Sep 23.
Article
en En
| MEDLINE
| ID: mdl-23933341
ABSTRACT
BACKGROUND:
VAR2CSA is a large polymorphic Plasmodium falciparum protein expressed on infected erythrocytes (IE) that allows their binding in the placenta, thus precipitating placental malaria (PM). The N-terminal part of VAR2CSA that contains the binding site to placental chondroitin sulfate A (CSA) is currently recognized as the most attractive region for vaccine development. An ultimate challenge is to define epitopes in this region that induce a broad cross-reactive adhesion inhibitory antibody response.METHODS:
Based on phylogenetic data that identified a dimorphic sequence motif in the VAR2CSA DBL2X, we raised antibodies against the NTS-DBL2X constructs containing one sequence or the other (3D7 and FCR3) and tested their functional properties on P. falciparum isolates from pregnant women and on laboratory-adapted strains.RESULTS:
The CSA binding inhibitory capacity of the antibodies induced varied from one parasite isolate to another (range, 10%100%), but the combined analysis of individual activity highlighted a broader functionality that increased the total number of isolates inhibited. Interestingly, the differential inhibitory effect of the antibodies observed on field isolates resulted in significant inhibition of all field isolates tested, suggesting that optimal inhibitory spectrum on field isolates from pregnant women might be achieved with antibodies targeting limited variants of the N-terminal VAR2CSA.CONCLUSIONS:
Our findings indicate that the NTS-DBL2X region of VAR2CSA can elicit strain-transcending anti-adhesion antibodies and suggest that the combination of the two major variants used here could represent the basis for an effective bivalent VAR2CSA-based vaccine.Palabras clave
BSA; CSA; CSPG; DBL; DSM; Duffy binding-like; IE; IPTp; Id; MFI; Malaria; N-terminal sequence; NTS; PBS; PM; PfEMP1; Pfalciparum-infected erythrocytes; Plasmodium falciparum; Plasmodium falciparum erythrocyte membrane protein 1; Pregnancy; VAR2CSA; Vaccine; bovine serum albumin; chondroitin sulfate A; chondroitin sulfate proteoglycan; dimorphic sequence motif; inter-domain; intermittent preventive treatment during pregnancy; median fluorescence intensity; phosphate buffered saline; placental malaria
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Plasmodium falciparum
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Anticuerpos Antiprotozoarios
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Adhesión Celular
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Eritrocitos
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Antígenos de Protozoos
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Animals
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Female
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Humans
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Pregnancy
Idioma:
En
Revista:
Vaccine
Año:
2013
Tipo del documento:
Article
País de afiliación:
Benín