A collaborative effort between researchers from Uganda, Tanzania, the US, Spain, and Denmark has resolved a longstanding question in malaria research: Do individuals living in regions with continuous malaria transmission develop broadly neutralizing antibodies (BnAbs) against the malaria parasite? The answer is yes. This discovery explains how antibody-mediated immunity develops against Plasmodium falciparum, the parasite responsible for the most severe forms of malaria. Importantly, the study reveals how immunity is possible despite the extensive variation in the parasite’s virulence genes, a puzzle that has baffled scientists for decades.

Batista Lab research fellow Raphael Reyes, PhD, was one of the authors of the paper before he joined the Ragon Institute.

The researchers found that broadly reactive antibodies from different individuals consistently bind to the same specific site on PfEMP1, a key virulence protein of P. falciparum. This epitope represents an “Achilles’ heel” of the parasite, as it cannot be altered without the parasite losing its ability to bind to the human receptor EPCR. PfEMP1 binding to EPCR is vital for the parasite’s survival and a key step in the development of severe malaria. Therefore, antibodies targeting this site effectively neutralize the parasite’s virulence, making it an ideal focus for vaccine development.

This breakthrough offers a promising pathway for developing improved malaria vaccines by mimicking the naturally acquired immunity seen in populations exposed to the disease. Advancements in vaccine and protein design, including novel AI technologies recently highlighted by the Nobel Prize in Chemistry, offer exciting opportunities to accelerate vaccine development for critical targets like the central epitopes of immunity to severe malaria discovered in this study.