Dissecting the antibody response to Plasmodium falciparum-infected erythrocytes

Antibodies that target red blood cells (RBCs) infected by the malaria parasite Plasmodium falciparum have been linked to protection against malaria, but these antibodies have not been well characterised, in part due to limitations of technology.

We have developed a technique that allows us to identify unusual antibodies containing parts of a protein called LAIR1 that target Plasmodium falciparum-infected RBCs. We will use this technology to study the antibodies that target infected RBCs in people from Mali who have been exposed to malaria. We will compare the antibodies of naturally protected and non-protected people to identify potential signatures of protection. We will then isolate cross-reactive antibodies that target diverse P. falciparum parasites and identify their targets as malaria vaccine candidates, and find more LAIR1-containing antibodies. We have found preliminary evidence that suggests that antibodies from some Malian people target RBCs infected by different P. falciparum parasites and that a sizable proportion (5 to 10 per cent) of these people possess antibodies that contain LAIR1.

This work will help to identify antibodies that protect people who are exposed to malaria, potentially including cross-reactive antibodies, against invariant  P. falciparum proteins. This may identify potential candidates for a malaria vaccine.