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

Autor:	McLean FE; Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom., Azasi Y; Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom., Sutherland C; Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom., Toboh E; Manhyia District Hospital, Kumasi, Ghana., Ansong D; Kwame Nkrumah University of Science and Technology, School of Medical Sciences, Kumasi, Ghana.; Departments of Child Health and Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana.; Malaria Research Centre, Agogo, Ghana., Agbenyega T; Kwame Nkrumah University of Science and Technology, School of Medical Sciences, Kumasi, Ghana.; Departments of Child Health and Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana.; Malaria Research Centre, Agogo, Ghana., Awandare G; West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Legon, Ghana., Rowe JA; Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Jazyk:	angličtina
Zdroj:	Infection and immunity [Infect Immun] 2024 Jul 11; Vol. 92 (7), pp. e0001524. Date of Electronic Publication: 2024 Jun 06.
DOI:	10.1128/iai.00015-24
Abstrakt:	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-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 recognizing 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 recognized by strain-transcending antibodies could be targeted therapeutically by monoclonal antibodies or vaccines. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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