Nine-year longitudinal study of antibodies to variant antigens on the surface of Plasmodium falciparum-infected erythrocytes - PubMed (original) (raw)

Nine-year longitudinal study of antibodies to variant antigens on the surface of Plasmodium falciparum-infected erythrocytes

H A Giha et al. Infect Immun. 1999 Aug.

Abstract

PfEMP1 is an antigenically variable molecule which mediates the adhesion of parasitized erythrocytes to a variety of cell types and which is believed to constitute an important target for naturally acquired protective immune responses in malaria. For 9 years we have monitored individuals living in an area of low-intensity, seasonal, and unstable malaria transmission in eastern Sudan, and we have used this database to study the acquisition, specificity, and duration of the antibody response to variant parasitized erythrocyte surface antigens. Both the levels and the spectrum of reactivity of these antibodies varied considerably among individuals, ranging from low levels of antibodies recognizing only few parasitized erythrocyte surface antigens to high levels of broad-specificity antibodies. In general, episodes of clinical malaria were associated with increases in the levels of parasitized erythrocyte surface-specific antibodies that subsided within months of the attack. This response was often, but not always, specific for the antigenic variants expressed by the parasite isolate causing disease. Our study provides evidence that Palciparum falciparum malaria is associated with a short-lived, variant-specific antibody response to PfEMP1-like antigens exposed on the surface of parasitized erythrocytes. Furthermore, our data suggest that the antigenic repertoires of variant antigens expressed by different parasite isolates show considerable overlapping, at least under Sahelian conditions of low-intensity, seasonal, and unstable malaria transmission. Finally, we demonstrate the existence of persistent differences among individuals in the capacity to mount antibody responses to variant surface antigens.

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Figures

FIG. 1

FIG. 1

Levels of plasma antibodies recognizing PfEMP1-like molecules on the surface of intact RBC infected with late developmental stages of P. falciparum as detected by flow cytometry. Data from nine parasite isolates (3D7 to FCR3 [columns]) tested versus plasma samples obtained in January 1996 from 37 individuals (E2 to 2N3 [rows]) from Daraweesh village, Sudan, are shown. Shading indicates antibody levels above background (mean + 2 standard deviations of samples from unexposed individuals). Numbers along the right and bottom edges of the figure indicate the number of positive data points per plasma sample and parasite isolate, respectively.

FIG. 2

FIG. 2

Long-term changes in levels of plasma antibodies recognizing PfEMP1-like molecules on the surface of intact RBC infected with late developmental stages of P. falciparum as detected by flow cytometry. The reactivity of plasma from three individuals selected for low (E2, left column), medium (2P4, center column), and high (2N3, right column) antibody levels with four parasite isolates collected in 1994 (S9457, top row), 1995 (Z453, second row; Z455, third row), and 1996 (Y372, bottom row) are shown. The x axis shows the date. The y axis shows the anti-PfEMP1-like antibody reactivity (mean flow cytometer channel number). The negative cutoff (mean + 2 standard deviations for five plasma samples from unexposed individuals) is shown as a dotted horizontal line. The level of anti-PfEMP1-like antibodies in a pool of hyperimmune plasma (positive control) is shown as a dashed horizontal line. Solid vertical lines indicate clinical episodes of malaria.

FIG. 3

FIG. 3

Long-term changes in levels of plasma antibodies recognizing PfEMP1-like molecules on the surface of intact RBC infected with late developmental stages of homologous and heterologous P. falciparum isolates as detected by flow cytometry. The reactivity of plasma from two individuals (P8 [left column] and P11 [right column]) with four parasite isolates collected in 1994 (S9457, top row), 1995 (Z453, second row; Z455, third row), and 1996 (Y372, bottom row) is shown. Isolates Z455 and Z453 were collected during clinical malaria attacks in November 1995 from individuals P8 and P11, respectively. Symbols are as in Fig. 2.

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