Decoding Antibodies from Malaria-Exposed Children Unveils Key Insights into Immunity

For the first time in scientific history, researchers have successfully decoded a naturally acquired antibody by sequencing it directly from the blood of a child exposed to malaria. Leveraging advanced mass spectrometry techniques, the research team identified an antibody that interferes with a crucial interaction between the Plasmodium falciparum parasite and human blood vessels—a process essential for the development of severe forms of malaria.

Malaria, caused by Plasmodium falciparum, remains a significant global health challenge, resulting in 600,000 deaths yearly, primarily young children in sub-Saharan Africa. Immunity to this severe form of malaria develops after multiple infections and is facilitated through antibodies that block the parasite's diversified PfEMP1 adhesion proteins from attaching to the human endothelial protein C receptor (EPCR) on blood vessel walls.

In a collaborative study, researchers from the National Institute for Medical Research in Tanzania and the University of Copenhagen discovered that individuals with immune plasma can prevent numerous diverse PfEMP1 variants from binding to EPCR. The findings were published in the prestigious journal Proceedings of the National Academy of Sciences.

The researchers utilized the REpAb antibody discovery platform to decipher the amino acid sequence of a monoclonal antibody possessing broad inhibitory activity against multiple PfEMP1 variants. This represents the first instance where mass spectrometry has been employed to recognize a functional plasma antibody that develops naturally following infection.

Collaborating with experts at The Scripps Research Institute in California, protein structural analysis unveiled how this broadly neutralizing antibody binds conserved residues across different PfEMP1 variants, effectively preventing parasite adhesion.

"Decoding the sequence of a naturally acquired antibody circulating within the bloodstream and observing its binding mechanism provides invaluable insights into the protective immune response against malaria," stated Senior Scientist Louise Turner from the Center for Translational Medicine and Parasitology at the University of Copenhagen.

"This breakthrough enables us to identify critical inhibitory antibodies directly in individuals who are naturally exposed to infection. This approach presents powerful opportunities for studying acquired antibody responses and advancing vaccine research," added Professor Thomas Lavstsen, also from the Center for Translational Medicine and Parasitology at the University of Copenhagen.

The study was conducted through a 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 in Denmark; the National Institute for Medical Research in Tanzania; Rapid Novor in Canada; and The Scripps Research Institute in California, USA.