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Infection and Immunity, December 2005, p. 7988-7995, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.7988-7995.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Neonatal and Maternal Immunological Responses to Conserved Epitopes within the DBL-{gamma}3 Chondroitin Sulfate A-Binding Domain of Plasmodium falciparum Erythrocyte Membrane Protein 1

Kim Brustoski,1,2 Martin Kramer,2 Ulrike Möller,2 Peter G. Kremsner,1,2 and Adrian J. F. Luty1,2*

Department of Parasitology, Institute for Tropical Medicine, University of Tübingen, D-72074 Tübingen, Germany,1 Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon2

Received 1 June 2005/ Returned for modification 9 July 2005/ Accepted 7 August 2005

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) mediates the adherence of P. falciparum-infected erythrocytes to placental syncytiotrophoblasts via interactions with chondroitin sulfate A (CSA), a characteristic of pregnancy-associated malaria. Pregnancy-associated malaria predicts increased susceptibility of newborns to malaria, and it is postulated that transplacental passage of parasite antigen induces immune regulatory activity in the neonate. We wished to examine the immune responsiveness to a CSA-binding domain of PfEMP1, the DBL-{gamma}3 domain, in cord and maternal venous blood obtained from pregnancies with various histories of P. falciparum infection. We assessed in vitro T-cell cytokine and plasma immunoglobulin G (IgG) and IgM responses to four peptides corresponding to highly conserved regions of a DBL-{gamma}3 domain common to central African parasite isolates. The presence of placental P. falciparum infection at delivery was associated with elevated frequencies of DBL-{gamma}3 peptide-specific CD3+ interleukin-10-positive T cells in cord blood, while treatment and clearance of infection prior to delivery was associated with elevated frequencies of CD3+ gamma interferon-positive T cells. DBL-{gamma}3 peptide-specific IgM antibodies were detected in 12 of 60 (20%) cord plasma samples from those born to mothers with P. falciparum infection during pregnancy. Consistent with polyclonal anti-PfEMP1 antibody responses that are associated with protection against pregnancy-associated malaria, the presence of maternal IgG antibodies with specificity for one of the DBL-{gamma}3 peptides showed a parity-dependent profile. These data demonstrate that peptides corresponding to conserved regions of the DBL-{gamma}3 domain of PfEMP1 are immunogenic in P. falciparum-infected mothers and their offspring.

* Corresponding author. Mailing address: Medical Parasitology, Department of Medical Microbiology, Radboud University, Nijmegen Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Phone: 31-(0)24-3613663. Fax: 31-(0)24-3614666. E-mail: a.luty{at}mmb.umcn.nl.

Editor: W. A. Petri, Jr.

Infection and Immunity, December 2005, p. 7988-7995, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.7988-7995.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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