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Infection and Immunity, June 2001, p. 3713-3718, Vol. 69, No. 6
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.6.3713-3718.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Antibodies to Variant Antigens on the Surfaces of Infected Erythrocytes Are Associated with Protection from Malaria in Ghanaian Children

Daniel Dodoo,1,2 Trine Staalsoe,2 Haider Giha,2,3 Jørgen A. L. Kurtzhals,1,2 Bartholomew D. Akanmori,1 Kojo Koram,1 Samuel Dunyo,1 Francis K. Nkrumah,1 Lars Hviid,2 and Thor G. Theander2,*

Immunology and Epidemiology Units, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana1; Centre for Medical Parasitology, Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), and Institute for Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark2; and Department of Biochemistry, University of Khartoum, Khartoum, Sudan3

Received 13 November 2000/Returned for modification 11 January 2001/Accepted 6 March 2001

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a variant antigen expressed on the surface of infected erythrocytes. Each parasite genome contains about 40 PfEMP1 genes, but only 1 PfEMP1 gene is expressed at a given time. PfEMP1 serves as a parasite-sequestering ligand to endothelial cells and enables the parasites to avoid splenic passage. PfEMP1 antibodies may protect from disease by inhibiting sequestration, thus facilitating the destruction of infected erythrocytes in the spleen. In this study, we have measured antibodies in Ghanaian children to a conserved region of PfEMP1 by enzyme-linked immunosorbent assay and antibodies to variant molecules on erythrocytes infected with field isolates of P. falciparum by flow cytometry. Based on close clinical monitoring, the children were grouped into those who did (susceptible) and those who did not (protected) have malaria during the season. The prevalences of antibodies to both the conserved PfEMP1 peptide and the variant epitopes were greater than 50%, and the levels of immunoglobulin G (IgG) correlated with age. The levels of antibodies to both the conserved peptide and the variant epitopes were higher in protected than in susceptible children. After correcting for the effect of age, the levels of IgG to variant antigens on a Sudanese and a Ghanaian parasite isolate remained significantly higher in protected than in susceptible children. Thus, the levels of IgG to variant antigens expressed on the surface of infected erythrocytes correlated with protection from clinical malaria. In contrast, the levels of IgG to a peptide derived from a conserved part of PfEMP1 did not correlate with protection from malaria.

* Corresponding author. Mailing address: Institute of Medical Microbiology and Immunology, University of Copenhagen, Panum Institute Building 24.2, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. Phone: 45 35 32 76 77. Fax: 45 35 32 78 51. E-mail: theander{at}biobase.dk.

Infection and Immunity, June 2001, p. 3713-3718, Vol. 69, No. 6
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.6.3713-3718.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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