Immunoglobulin G Isotype Responses to Erythrocyte Surface-Expressed Variant Antigens of Plasmodium falciparum Predict Protection from Malaria in African Children

Abstract

We assessed immunoglobulin G (IgG) isotype responses to variant surface antigens (VSA) expressed on parasite-infected erythrocytes of a panel of heterologous isolates during and after acute episodes in groups of Gabonese children presenting with either mild or severe Plasmodium falciparum malaria. In the acute and convalescent phases IgG3 and IgG1 anti-VSA antibodies, respectively, predominated. In the absence of infection, the levels of both cytophilic isotypes waned, while those of IgG4 increased, particularly in those admitted with severe malaria. Prospective analyses showed significantly longer delays between malaria attacks associated both (i) with increasing IgG1 responses with specificity for VSA of isolates from children with mild malaria and (ii) with increasing IgG4 responses with specificity for VSA of isolates from children with severe malaria. These findings imply that the predictive value of prospectively measured cross-reactive VSA-specific IgG antibodies with respect to protection against malaria in African children depends both on their isotype and on their fine specificity

IgG isotypic antibodies to crude <i>Plasmodium falciparum</i> blood-stage antigen associated with placental malaria infection in parturient Cameroonian women

“…Studies have shown that the responses for both non-VSA-PAM 13,14 and VSAPAM [10][11][12][13][14][15] are dominated by the cytophilic subclass IgG1, followed by IgG3 consistent with data obtained from non-pregnant adults and children 14,16,17 . The predominance of IgG1 and IgG3 cytophilic antibody in endemic areas has been associated with either lower parasitaemia 18 or a lower risk of malaria attack 19 .…”

Placental Malaria Induces Variant-Specific Antibodies of the Cytophilic Subtypes Immunoglobulin G1 (IgG1) and IgG3 That Correlate with Adhesion Inhibitory Activity

“…In Kenyan children, antibodies to VSA expressed by autologous parasites were predominantly IgG3 (16). In Gabon, anti-VSA antibodies of the IgG3 subtype were prominent among healthy adults and children (7), and anti-VSA IgG1 and IgG3 were associated with acute malaria infection in children (26).…”

“…It is the cytophilic subtypes of antibodies targeting merozoite surface antigens that are associated with clinical and parasitological immunity (for a review, see reference 14), presumably because interaction of anti-merozoite antibodies with Fc receptors plays a critical role. The few studies which have examined the isotype profile of antibodies specific for VSA in nonpregnant individuals suggest that anti-VSA antibodies are also predominantly cytophilic (7,16,18,26).…”

Priming of CD4+ T cells and development of CD4+ T cell memory; lessons for malaria

“…Thus the repeat infection takes place in a different cytokine milieu. This also appears to be the case in humans (30), and may contribute to anti‐disease immunity, because IL‐10 is critical to tip the cytokine balance away from disease (31). Ongoing work will be focused on determining whether there is a malaria‐specific defect in memory cell differentiation or survival in the mouse model.…”