Induction of adhesion-inhibitory antibodies against placental Plasmodium falciparum parasites by using single domains of VAR2CSA

TY - JOUR

T1 - Induction of adhesion-inhibitory antibodies against placental Plasmodium falciparum parasites by using single domains of VAR2CSA

AU - Nielsen, Morten A

AU - Pinto, Vera V

AU - Resende, Mafalda

AU - Dahlbäck, Madeleine

AU - Ditlev, Sisse B

AU - Theander, Thor G

AU - Salanti, Ali

N1 - Keywords: Animals; Antibodies, Protozoan; Antigens, Protozoan; Cell Adhesion; Humans; Malaria Vaccines; Plasmodium falciparum; Rats; Trophoblasts; Vaccines, Subunit

PY - 2009

Y1 - 2009

N2 - In areas of endemicity pregnancy-associated malaria is an important cause of maternal anemia, stillbirth, and delivery of low-birth-weight children. The syndrome is precipitated by the accumulation of Plasmodium falciparum-infected erythrocytes in the placenta, mediated through an interaction between a parasite protein expressed on erythrocytes named variant surface antigen 2-chondroitin sulfate A (VAR2CSA) and CSA on syncytiotrophoblasts. VAR2CSA is a large polymorphic protein consisting of six Duffy binding-like (DBL), domains and with current constraints on recombinant protein production it is not possible to produce entire VAR2CSA recombinant proteins. Furthermore, the presence of polymorphisms has raised the question of whether it is feasible to define VAR2CSA antigens eliciting broadly protective antibodies. Thus, the challenge for vaccine development is to define smaller parts of the molecule which induce antibodies that inhibit CSA binding of different parasite strains. In this study, we produced a large panel of VAR2CSA proteins and raised antibodies against these antigens. We show that antibodies against the DBL4 domain effectively inhibit parasite binding. As the inhibition was not limited to homologous parasite strains, it seems feasible to base a protective malaria vaccine on a single VAR2CSA DBL domain.

AB - In areas of endemicity pregnancy-associated malaria is an important cause of maternal anemia, stillbirth, and delivery of low-birth-weight children. The syndrome is precipitated by the accumulation of Plasmodium falciparum-infected erythrocytes in the placenta, mediated through an interaction between a parasite protein expressed on erythrocytes named variant surface antigen 2-chondroitin sulfate A (VAR2CSA) and CSA on syncytiotrophoblasts. VAR2CSA is a large polymorphic protein consisting of six Duffy binding-like (DBL), domains and with current constraints on recombinant protein production it is not possible to produce entire VAR2CSA recombinant proteins. Furthermore, the presence of polymorphisms has raised the question of whether it is feasible to define VAR2CSA antigens eliciting broadly protective antibodies. Thus, the challenge for vaccine development is to define smaller parts of the molecule which induce antibodies that inhibit CSA binding of different parasite strains. In this study, we produced a large panel of VAR2CSA proteins and raised antibodies against these antigens. We show that antibodies against the DBL4 domain effectively inhibit parasite binding. As the inhibition was not limited to homologous parasite strains, it seems feasible to base a protective malaria vaccine on a single VAR2CSA DBL domain.

U2 - 10.1128/IAI.00159-09

DO - 10.1128/IAI.00159-09

M3 - Journal article

C2 - 19307213

SN - 0019-9567

VL - 77

SP - 2482

EP - 2487

JO - Infection and Immunity

JF - Infection and Immunity

IS - 6

ER -