Acquired Antibodies to Merozoite Antigens in Children from Uganda with Uncomplicated or Severe Plasmodium falciparum Malaria

Abstract

Malaria can present itself as an uncomplicated or severe disease. We have here studied the quantity and quality of antibody responses against merozoite antigens, as well as multiplicity of infection (MOI), in children from Uganda. We found higher levels of IgG antibodies toward erythrocyte-binding antigen EBA181, MSP2 of Plasmodium falciparum 3D7 and FC27 (MSP2-3D7/ FC27), and apical membrane antigen 1 (AMA1) in patients with uncomplicated malaria by enzyme-linked immunosorbent assay (ELISA) but no differences against EBA140, EBA175, MSP1, and reticulocyte-binding protein homologues Rh2 and Rh4 or for IgM against MSP2-3D7/FC27.Patients with uncomplicated malaria were also shown to have higher antibody affinities for AMA1 by surface plasmon resonance (SPR). Decreased invasion of two clinical P. falciparum isolates in the presence of patient plasma correlated with lower initial parasitemia in the patients, in contrast to comparisons of parasitemia to ELISA values or antibody affinities, which did not show any correlations. Analysis of the heterogeneity of the infections revealed a higher MOI in patients with uncomplicated disease, with the P. falciparum K1 MSP1 (MSP1-K1) and MSP2-3D7 being the most discriminative allelic markers. Higher MOIs also correlated positively with higher antibody levels in several of the ELISAs. In conclusion, certain antibody responses and MOIs were associated with differences between uncomplicated and severe malaria. When different assays were combined, some antibodies, like those against AMA1, seemed particularly discriminative. However, only decreased invasion correlated with initial parasitemia in the patient, signaling the importance of functional assays in understanding development of immunity against malaria and in evaluating vaccine candidates.

Natural antibody responses to Plasmodium falciparum MSP3 and GLURP(R0) antigens are associated with low parasite densities in malaria patients living in the Central Region of Ghana

“…There was no significant difference in MOI determined by either msp1 or msp2 genotyping among the three age groups studied (Fig. 4 ), which is consistent with recent reports from Sudan [ 35 ], Uganda [ 36 ] and Ethiopia [ 32 ]. Although there was a significant relationship between MOI and parasite density which was not observed in the Ethiopian study [ 32 ].…”

Host age and expression of genes involved in red blood cell invasion in Plasmodium falciparum field isolates

“…PfRh2 2030–2528 and regions III–V of EBA175 (EBA175 III–V ) and EBA140 (EBA140 III–V ) were produced at the Burnet Institute 26, 43, 44 . Recombinant proteins were expressed in Escherichia coli .…”

Subclass responses and their half-lives for antibodies against EBA175 and PfRh2 in naturally acquired immunity against Plasmodium falciparum malaria

“…The recombinant merozoite antigens used in this study have been described in detail previously [ 44 ]. In brief, regions III to V of EBA175 (3D7; aa 761 to 1298) [ 19 ] and PfRh2A9 (3D7; aa 2027 to 2533, common region for both PfRh2a and PfRh2b) [ 42 ] were expressed in E. coli as GST-tagged fusion proteins.…”