Malaria

Keeping plasmodia out of erythrocytes

Malaria is one of the most devastating infectious diseases throughout human history. Each year, more than 200 million new cases are occurring worldwide. More than 400 000 people die from Malaria each year, two thirds of which are still in their childhood. The disease is particularly widespread in developing countries within tropical regions, with more than 90% of malaria-associated deaths occurring in Africa. Individuals at particularly high risk include children, pregnant women, travelers, and immunocompromised patients.



The disease is caused by plasmodia, among which Plasmodium falciparum (Pf) accounts for the vast majority (>99%) of malaria-related deaths. When an infected Anopheles mosquito bites a person, Pf sporozoites are released and reach the liver, where they replicate to release merozoites to the blood. Merozoites then infect erythrocytes (red blood cells), causing repeated cycles of replication, erythrocyte disruption, and release. Moreover, infected erythrocytes have a higher tendency to stick to endothelial cells, causing the obstruction of capillaries. Symptoms include fever and headache, with complications such as anemia, respiratory distress, kidney failure, and encephalopathy.

Thus, a crucial step in the life cycle of Pf, as well as in the pathogenesis of malaria, consists in the entry of merozoites into red blood cells. This entry is enabled by the specific interaction of protein molecules. Preventing these interactions represents an attractive option to halt the infection and combat the disease.

We are developing nanobodies against the proteins that mediate the entry of Pf merozoites into red blood cells. Covering these proteins with nanobodies will prevent the entry of Pf merozoites into erythrocytes. We hope to bring such nanobodies to the clinics for successful malaria therapy and to eliminate Pf even despite resistance to currently available therapeutics.

Targeting entry factors through nanobodies and next-generation vaccines is thus aiming at the sustainable prevention and therapy of otherwise treatment-resistant malaria.