Trends in Microbiology
Volume 10, Issue 2, 1 February 2002, Pages 55-58
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Research update
The role of antibodies to Plasmodium falciparum-infected-erythrocyte surface antigens in naturally acquired immunity to malaria

https://doi.org/10.1016/S0966-842X(01)02278-8Get rights and content

Abstract

Plasmodium falciparum, the most virulent species of human malaria parasite, causes 1–3 million deaths per year. Because this parasite is susceptible to naturally acquired host immunity the main burden of disease falls on young children. The mechanism of this immunity is still unclear. However, the parasite makes a considerable investment in the insertion of highly polymorphic antigens (parasite-infected-erythrocyte surface antigens, PIESA) on the infected erythrocyte surface, and these antigens are potentially important immune targets.

Section snippets

Diverse parasite antigens are expressed on the infected erythrocyte surface

The identification of specific host immune responses and molecular targets that explain these characteristics of immunity would clearly contribute greatly to both an understanding of the biology of the parasite–host interaction and to the development of vaccines. For this reason, there has been a long-standing interest in parasite proteins that are expressed either on the parasite surface or on the surface of the cells that they invade 6, 7. Here, we will concentrate on the surface of

Are PIESA targets for naturally acquired immunity?

This question has been addressed in three ways.

In an early longitudinal study in the Gambia [14], the titre of PIESA antibodies was shown to be the only one of a series of immune assays that was associated with subsequent protection against disease. More recent studies have given variable results. The ability of sera to recognize PIESA in an isolate from Kenya was not associated with any protection from disease in Kenya [15]. In Sudan [16], PIESA antibodies to a Ghanaian parasite isolate were

A molecular basis for PIESA diversity

At the molecular level there are abundant data that could explain why PIESA are diverse. PfEMP1, the best characterized constituent of PIESA, is encoded by ∼50 ‘var’ genes per genome and undergoes rapid clonal antigenic variation [9] through a poorly understood process of coordinated gene expression [19]. Furthermore, the majority of var genes are situated in the unstable sub-telomeric areas of most chromosomes and can undergo non-homologous recombination during both meiosis and mitosis 20, 21.

Placental malaria as a model for future studies on immunity to severe malaria

Recent work on placental malaria illustrates both the interplay between function and antigenicity and the potential usefulness of PfEMP1 as a vaccine target.

Women in their first pregnancy are particularly susceptible to malaria infections of their placenta and this is an important cause of severe anaemia in women and of low birthweight in children. However, immunity develops rapidly during subsequent pregnancies and this immunity is associated with the development of antibodies to a restricted,

Acknowledgements

This article is published with permission of the Director of The Kenya Medical Research Institute. We thank the Wellcome Trust for funding under a Senior Fellowship (K.M.) and an Advanced Training Fellowship in Tropical Medicine (P.B.). Thanks to Sue Kyes, Paul Horrocks, Leann Tilley, Britta Urban, Barry Elford and Andy Leisewitz for comments on the manuscript.

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