Detection of naturally acquired, strain-transcending antibodies against rosetting Plasmodium falciparum strains in humans

Florence E. McLean, Yvonne Azasi, Cameron Sutherland, Emmanuel Toboh, Daniel Ansong, Tsiri Agbenyega, Gordon Awandare, J. Alexandra Rowe*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Strain-transcending antibodies against virulence-associated subsets of P. falciparum infected erythrocyte 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-mediating Plasmodium falciparum Erythrocyte 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, we tested plasma from 80 individuals living in malaria-endemic regions for IgG recognition of the surface of four P. falciparum rosetting strains using flow cytometry. 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 35 transcending antibodies. We found that seroprevalence (percentage of positive plasma samples) against allopatric rosetting strains was high in adults (63%-93%) but lower in children (13%-48%). 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 rosetting P. falciparum strains 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 by monoclonal antibodies or vaccines.
Original languageEnglish
Number of pages39
JournalInfection and Immunity
Publication statusAccepted/In press - 30 Apr 2024

Keywords / Materials (for Non-textual outputs)

  • severe malaria
  • PfEMP1
  • rosette formation
  • virulence
  • immunology
  • antibodies
  • epitopes

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