Expressed var gene repertoire and variant surface antigen diversity in a shrinking Plasmodium falciparum population

Abstract

The var gene-encoded erythrocyte membrane protein-1 of Plasmodium falciparum (PfEMP-1) is the main variant surface antigen (VSA) expressed on infected erythrocytes. The rate at which antibody responses to VSA expressed by circulating parasites are acquired depends on the size of the local VSA repertoire and the frequency of exposure to new VSA. Because parasites from areas with declining malaria endemicity, such as the Amazon, typically express a restricted PfEMP-1 repertoire, we hypothesized that Amazonians would rapidly acquire antibodies to most locally circulating VSA. Consistent with our expectations, the analysis of 5878 sequence tags expressed by 10 local P. falciparum samples revealed little PfEMP-1 DBL1α domain diversity. Among the most commonly expressed DBL1α types, 45% were shared by two or more independent parasite lines. Nevertheless, Amazonians displayed major gaps in their repertoire of anti-VSA antibodies, although the breadth of anti-VSA antibody responses correlated positively with their cumulative exposure to malaria. We found little antibody cross-reactivity even when testing VSA from related parasites expressing the same dominant DBL1α types. We conclude that variant-specific immunity to P. falciparum VSAs develops slowly despite the relatively restricted PfEMP-1 repertoire found in low-endemicity settings.

Molecular epidemiology of continued Plasmodium falciparum disease transmission after an outbreak in Ecuador

“…Supporting this view, prior network analyses and computational models combining evolution and epidemiology point to variant-specific immune selection defining var population structure even in low transmission, albeit to a much lesser extent than expected in high-transmission settings where selection acts strongly against recombinant or highly related repertoires due to cross-immunity (37, 64). The availability of var DBLa sequences provides the potential to test this hypothesis by serological methods that measure variant-specific immunity, as shown in serological studies in Papua New Guinea (65) and the Brazilian Amazon (66). In addition, characterization of antigenic variant var DBLa sequences could be leveraged in future gene expression studies to understand parasite virulence.…”

Immunoproteomics of Plasmodium falciparum-infected red blood cell membrane fractions

“…The resulting gels were maintained in 20% ammonium sulphate until spots were picked. Patient sera were obtained as per the methods described by Medeiros et al (2013) and Carlos et al (2016) . Western blotting was performed using 1:1000 dilutions of pooled patient sera.…”