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Infection and Immunity, June 2009, p. 2482-2487, Vol. 77, No. 6
0019-9567/09/$08.00+0     doi:10.1128/IAI.00159-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Induction of Adhesion-Inhibitory Antibodies against Placental Plasmodium falciparum Parasites by Using Single Domains of VAR2CSA{triangledown}

Morten A. Nielsen, Vera V. Pinto, Mafalda Resende, Madeleine Dahlbäck, Sisse B. Ditlev, Thor G. Theander, and Ali Salanti*

Centre for Medical Parasitology at Department of International Health, Immunology, and Microbiology, University of Copenhagen, and at Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark

Received 11 February 2009/ Returned for modification 3 March 2009/ Accepted 15 March 2009

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.

* Corresponding author. Mailing address: CMP, Øster Farimagsgade 5, Building 22, PO 2099, 1014 Copenhagen, Denmark. Phone: 45 35327676. Fax: 45 35327851. E-mail: salanti{at}sund.ku.dk

{triangledown} Published ahead of print on 23 March 2009.

Editor: W. A. Petri, Jr.

Infection and Immunity, June 2009, p. 2482-2487, Vol. 77, No. 6
0019-9567/09/$08.00+0     doi:10.1128/IAI.00159-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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