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Infection and Immunity, June 2004, p. 3531-3535, Vol. 72, No. 6
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.6.3531-3535.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Geographical and Temporal Conservation of Antibody Recognition of Plasmodium falciparum Variant Surface Antigens

Morten A. Nielsen,1 Lasse S. Vestergaard,1 John Lusingu,2 Jørgen A. L. Kurtzhals,1 Haider A. Giha,3 Berit Grevstad,1 Bamenla Q. Goka,4 Martha M. Lemnge,2 James B. Jensen,5 Bartholomew D. Akanmori,6 Thor G. Theander,1 Trine Staalsoe,1 and Lars Hviid1*

Centre for Medical Parasitology at Department of Infectious Diseases and Department of Clinical Microbiology, Copenhagen University Hospital (Rigshospitalet) and Institute for Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark,1 National Institute for Medical Research, Amani, Tanzania,2 Department of Biochemistry, University of Khartoum, Khartoum, Sudan,3 Department of Child Health, Korle-Bu Teaching Hospital, University of Ghana, Accra, Ghana,4 Department of Microbiology, Brigham Young University, Provo, Utah,5 Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana6

Received 22 October 2003/ Returned for modification 9 December 2003/ Accepted 24 December 2003

The slow acquisition of protection against Plasmodium falciparum malaria probably reflects the extensive diversity of important antigens. The variant surface antigens (VSA) that mediate parasite adhesion to a range of host molecules are regarded as important targets of acquired protective immunity, but their diversity makes them questionable vaccine candidates. We determined levels of VSA-specific immunoglobulin G (IgG) in human plasma collected at four geographically distant and epidemiologically distinct localities with specificity for VSA expressed by P. falciparum isolates from three African countries. Plasma levels of VSA-specific IgG recognizing individual parasite isolates depended on the transmission intensity at the site of plasma collection but were largely independent of the geographical origin of the parasites. The total repertoire of immunologically distinct VSA thus appears to be finite and geographically conserved, most likely due to functional constraints. Furthermore, plasma samples frequently had high IgG reactivity to VSA expressed by parasites isolated more than 10 years later, showing that the repertoire is also temporally stable. Parasites from patients with severe malaria expressed VSA (VSASM) that were better recognized by plasma IgG than VSA expressed by other parasites, but importantly, VSASM-type antigens also appeared to show substantial antigenic homogeneity. Our finding that the repertoire of immunologically distinct VSA in general, and in particular that of VSASM, is geographically and temporally conserved raises hopes for the feasibility of developing VSA-based vaccines specifically designed to accelerate naturally acquired immunity, thereby enhancing protection against severe and life-threatening P. falciparum malaria.

* Corresponding author. Mailing address: Department of Infectious Diseases M7641, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark. Phone: 45 35 45 79 57. Fax: 45 35 45 76 44. E-mail: lhcmp{at}rh.dk.

Editor: W. A. Petri, Jr.

Infection and Immunity, June 2004, p. 3531-3535, Vol. 72, No. 6
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.6.3531-3535.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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