Detection of naturally acquired, strain-transcending antibodies against rosettingPlasmodium falciparumstrains in humans

Abstract

AbstractStrain-transcending antibodies against subsets ofP. falciparumblood stage surface antigens could protect children from severe malaria. However, the evidence supporting the existence of such antibodies is incomplete and inconsistent. One subset of surface antigens associated with severe malaria, rosette-mediatingPlasmodium falciparumErythrocyte Membrane Protein one (PfEMP1) variants, cause infected erythrocytes to bind to uninfected erythrocytes to form clusters of cells (rosettes) that contribute to microvascular obstruction and pathology. Here, using flow cytometry of live infected erythrocytes, we tested plasma from 80 individuals living in malaria-endemic regions for IgG recognition of the surface of fourP. falciparumrosetting strains. Broadly-reactive plasma samples were then used in antibody elution experiments in which intact IgG was eluted from the surface of infected erythrocytes and transferred to heterologous rosetting strains to look for strain-transcending antibodies. We found that seroprevalence (percentage of samples that recognised each strain) against allopatric rosetting strains was high in adults (58% - 93%), but lower in children (5%-30%). Strain-transcending antibodies were present in nine out of eleven eluted antibody experiments, with six of these recognising multiple heterologous rosetting parasite strains. One eluate had rosette disrupting activity against heterologous strains, suggesting PfEMP1 as the likely target of the strain-transcending antibodies. Naturally acquired strain-transcending antibodies to rosettingP. falciparumstrains in humans have not been directly demonstrated previously. Their existence suggests that such antibodies could play a role in clinical protection and raises the possibility that conserved epitopes recognised by strain-transcending antibodies could be targeted therapeutically.