Malaria parasites must first infect the liver before they can cause disease. Scientists from the Laboratory of Medical Biochemistry (University of Antwerp) and the Centre d’immunologie et des maladies infectieuses (Sorbonne Université, Inserm, CNRS) combined structural modelling, electron microscopy, small-angle X-ray scattering at the SOLEIL beamline and antibody neutralization assays to investigate two key Plasmodium sporozoite proteins, P36 and P52.
Their results suggest that P36 and P52 form a complex that can be targeted by neutralizing antibodies, preventing infection of liver cells. These proteins could therefore represent promising targets for new antimalarial strategies.
Malaria is caused by parasites of the genus Plasmodium, which are transmitted through the bite of infected Anopheles mosquitoes that inject parasite stages known as sporozoites (SPZs) into the host skin. SPZs migrate to and infect the host liver for an initial round of multiplication. SPZs and liver stages have long been considered as ideal targets for malaria vaccines as targeting these stages can prevent disease onset.
During the parasite’s life cycle a multitude of stage-specific surface proteins are involved in a variety of important processes. The main SPZ surface protein, the circumsporozoite protein (CSP), is the target of currently approved malaria vaccines and preventive antibody therapies. Studies in mouse malaria models have shown that antibodies against CSP protect mainly by stopping the parasite in the skin. However, some of the most effective antibodies also provide protection against the parasite in the bloodstream and liver. Other SPZ proteins involved at different steps of the infection process may thus represent additional targets for protection.
Read more on the SOLEIL website
Image: Diagram showing the two possible binding sites for antibodies on the heterodimer, depending on the position of the tag, and the resulting inhibitory—or non-inhibitory—effect of these antibodies on the invasion of liver cells.