Immunoglobulin G antibody reactivity to a group A Plasmodium falciparum erythrocyte membrane protein 1 and protection from P. falciparum malaria

Abstract

Variant surface antigens (VSA) on the surface of Plasmodium falciparum-infected red blood cells play a major role in the pathogenesis of malaria and are key targets for acquired immunity. The best-characterized VSA belong to the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family. In areas where P. falciparum is endemic, parasites causing severe malaria and malaria in young children with limited immunity tend to express semiconserved PfEMP1 molecules encoded by group A var genes. Here we investigated antibody responses of Tanzanians who were 0 to 19 years old to PF11_0008, a group A PfEMP1. PF11_0008 has previously been found to be highly transcribed in a nonimmune Dutch volunteer experimentally infected with NF54 parasites. A high proportion of the Tanzanian donors had antibodies against recombinant PF11_0008 domains, and in children who were 4 to 9 years old the presence of antibodies to the PF11_0008 CIDR2beta domain was associated with reduced numbers of malaria episodes. These results indicate that homologues of PF11_0008 are present in P. falciparum field isolates and suggest that PF11_0008 CIDR2beta-reactive antibodies might be involved in protection against malaria episodes.

FIG. 1.

Point prevalence (circles and error bars showing 95% confidence intervals) and plasma levels (bars and error bars showing geometric means and 95% confidence intervals) of IgG antibodies to PF11_0008 DBL1α, DBL2γ, and CIDR2β domains. Plasma was collected from individuals who were 2 to 19 years old living in Mgome (high malaria transmission) (A), Ubiri (moderate malaria transmission) (B), or Magamba (low malaria transmission) (C).

FIG. 2.

Point prevalence (circles and error bars showing 95% confidence intervals) and plasma levels (bars and error bars showing geometric means and 95% confidence intervals) of IgG antibodies reacting to DBL1α (A), DBL2γ (B), and CIDR2β (C) of PF11_0008. Plasma was collected from individuals who were 0 to 19 years old living in Mkokola, a village where the level of malaria transmission is high.

FIG. 3.

P. falciparum geometric mean density (bars and error bars showing 95% confidence intervals) and percentage of children and adults with a malaria episode in a high-malaria-transmission village (Mkokola) as defined by fever and the presence of parasites (circles and error bars showing 95% confidence intervals).

FIG. 4.

PF11_0008 CIDR2β IgG levels in individuals with (shaded box plots) or without (open box plots) a malaria episode in different age groups in Mkokola. The IgG levels are indicated by box plots with the median and the 25th and 75th percentiles; the error bars indicate the 10th and 90th percentiles, and the circles indicate outliers. P values calculated using the two-sample t test with equal variances are indicated.