Colorized electron micrograph showing malaria parasite (right, blue) attaching to a human red blood cell. The inset shows a detail of the attachment point at higher magnification. Credit: NIAID

In a scientific first, researchers have decoded a naturally acquired antibody directly from the blood of a child exposed to malaria. Using advanced mass spectrometry, the team identified an antibody that blocks a critical interaction between the parasite Plasmodium falciparum and human blood vessels—a step central to the development of severe malaria.

Malaria, caused by Plasmodium falciparum, remains a major global health threat, claiming 600, 000 lives annually, mostly young children in sub-Saharan Africa. Immunity to severe malaria develops after repeated infections and is mediated by antibodies blocking the parasite's highly diversified PfEMP1 adhesion proteins from binding to the human endothelial protein C receptor (EPCR) on blood vessel walls.

In the collaborative study, researchers from the National Institute for Medical Research in Tanzania and the University of Copenhagen have identified that donors with immune plasma are able to prevent many diverse PfEMP1 variants from binding to EPCR. The paper is published in the journal Proceedings of the National Academy of Sciences.

The researchers used the REpAb antibody discovery platform to uncover the amino acid sequence of a monoclonal antibody with broad inhibitory activity against diverse PfEMP1 variants. This is the first time mass spectrometry has been applied to identify a functional plasma antibody developed naturally after infection.

Protein structural analysis, carried out with researchers at The Scripps Research Institute in California, revealed how this broadly neutralizing antibody binds to conserved residues across different PfEMP1 variants to block parasite adhesion.

"By sequencing a naturally acquired antibody circulating in the blood and seeing exactly how it binds, we gain valuable insight into the protective antibody response against malaria, " explains Senior Scientist, Louise Turner, Center for Translational Medicine and Parasitology, University of Copenhagen.

"We can now identify functionally significant inhibitory antibodies directly from individuals naturally exposed to infection. This provides a powerful way to study naturally acquired antibody responses and generate leads for our vaccine research, " says Professor Thomas Lavstsen, Center for Translational Medicine and Parasitology, University of Copenhagen.

The study was carried out in collaboration between the Center for Translational Medicine and Parasitology, Department of Immunology and Microbiology at the University of Copenhagen and Department of Infectious Diseases, Rigshospitalet, Denmark; the National Institute for Medical Research, Tanzania; Rapid Novor, Canada; and the Scripps Research Institute California, U.S.

More information: Turner, Louise et al, Identification of broadly inhibitory anti-PfEMP1 antibodies by mass spectrometry sequencing of plasma IgG from a malaria-exposed child, Proceedings of the National Academy of Sciences (2025). DOI: 10.1073/pnas.2508744122. doi.org/10.1073/pnas.2508744122  Journal information: Proceedings of the National Academy of Sciences