Structure of Plasmodium vivax P25 and its complex with transmission-blocking antibody

School of Life Sciences, Jawaharlal Nehru University* National Institutes of Health**
â—‹ajay kumar saxena* K Singh** H P Su** M M Klein** A W Stower** A J Saul** C Long** D N Garboczi**

Malaria parasites must infect the mosquito to complete their life cycle. In vertebrates, they inhabit a protected niche inside red blood cells. But when a parasite exits the red blood cell in the mosquito gut, it becomes exposed to the mosquito's digestion and innate immune responses. During the first 24 hours outside the red blood cell, P25 and P28 proteins cover the surface of the parasite, while the parasite develops into a form that can exit the gut. As it moves through the mosquito gut and gut epithelial wall, the abundant P25 and P28 proteins are continually shed from the parasite. Antibodies (and their Fab fragments) against P25 or P28 prevent parasites from exiting the gut without inhibiting locomotion. At present, the mosquito's defenses against Plasmodium are under intense study as we realize that only a few vulnerable, yet surviving parasites are responsible for the infection of the mosquito salivary glands. P25 is in clinical trial as a vaccine that will elicit antibodies that block the transmission of malaria.

Our structures reveal the shape of the members of the P25/P28 families of Plasmodium proteins and show a loop, at the vertex of the P25/P28 triangle, where antibodies bind that prevent the transmission of malaria through the mosquito. The structures that we describe will stimulate new knowledge of the basic biology of the parasite in the mosquito and the development of drugs and vaccines against the vulnerable mosquito stage of the malaria parasite.