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VAR2CSA and protective immunity against pregnancy-associated Plasmodium falciparum malaria

Published online by Cambridge University Press:  25 October 2007

L. HVIID*
Affiliation:
Centre for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark
A. SALANTI
Affiliation:
Centre for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark
*
Address for correspondence: Lars Hviid, Centre for Medical Parasitology, Department of Infectious Diseases M4701, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark. Fax +45 35 32 78 51. E-mail: lhcmp@rh.dk

Summary

People living in areas with stable transmission of P. falciparum parasites acquire protective immunity to malaria over a number of years and following multiple disease episodes. Immunity acquired this way is mediated by IgG with specificity for parasite-encoded, clonally variant surface antigens (VSA) on the surface of infected erythrocytes (IEs). However, women in endemic areas become susceptible to P. falciparum infection when they become pregnant, particularly for the first time, regardless of previously acquired protective immunity. This conundrum was resolved when it was observed that the selective placental accumulation of IEs that characterizes pregnancy-associated malaria (PAM) is caused by an immunologically and functionally unique subset of VSA (VSAPAM) that is only expressed by parasites infecting pregnant women, and that protective immunity to PAM is mediated by IgG with specificity for VSAPAM. In this review we summarize the research leading to the identification of the distinctly structured PfEMP1 variant VAR2CSA as the dominant PAM-type VSA and as the clinically most important target of the protective immune response to placental P. falciparum infection.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2007

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References

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