Structures reveal new target for malaria vaccine

The discovery paves the way for the development of a more effective and practical human vaccine for malaria, a disease responsible for half a million deaths worldwide each year.

Malaria kills about 445,000 people a year, mostly young children in sub-Saharan Africa, and sickens more than 200 million. It’s caused by a parasite, Plasmodium falciparum (Pf), and is spread to humans through the bite of an infected Anopheles mosquito.

The parasite’s complex life cycle and rapid mutations have long challenged vaccine developers. Only one experimental vaccine, known as RTS,S, has progressed to a Phase 3 clinical trial (testing on large groups of people for efficacy and safety). To elicit an immune response, this vaccine uses a fragment of circumsporozoite protein (CSP), which covers the malaria parasite in its native conformation. However, the trial results showed that RTS,S is only moderately effective, protecting about one-third of the young children who received it over a period of four years.

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Image (a) Left: Surface representation of CIS43 (light chain in tan and heavy chain in light blue), with peptide 21 shown as sticks (purple). Right: A 90° rotation of the representation. See entire image here.