Pre-erythrocytic phase of malaria : infection and immunity
Former research by the laureate
Robert Menard is investigating how the malaria parasite develops in the skin and the liver before reaching the red blood cells (the pre-rythrocytic phase). His goal with his team is to identify parasite products important for the key steps of the infection and to decipher protection mechanisms in that phase, and to identify to new protective antigens to develop a vaccine.
Introduction
Malaria remains the most severe parasitic disease in the world. Half of the world population is at risk, and up to a million people die from it each year, mostly young children in Sub saharen Africa. The etiological agent for malaria is a unicellular eukaryote called Plasmodium.
The malaria infection is systematically divided in two phases. The first one, called the pre-erythrocytic one, follows the injection of parasites by the vector mosquito. During this asymptomatic phase, parasites are injected in the skin and reach the liver to invade hepatocytes and multiply into new parasitic forms which will then invade erythrocytes. The second phase, responsible for all of the symptoms and complications of the disease, corresponds to the erythrocytes infection by the parasites and goes on in repeated cycles.
The goal of Robert Ménard’s research is to better understand the pre-erythrocytic phase of the malaria infection.
Projects
Robert Ménard and his team are pursuing several research axes.
1/ They are aiming at getting a global and in situ understanding of the pre-erythrocitic phase, using a rodent model and intravital imaging tools in mouse. Those studies led him and his group to uncover multiple unexpected aspects of the infection, particularly the complete parasite development in skin cells, the infection of the lymph node draining the injection site, as well as host innate immunity escape mechanisms like the crossing of phagocytes in the skin and the liver.
2/ They are deciphering at the molecular level some essential abilities of the parasite, notably its mobility and host cell invasion abilities. Plasmodium’s mobility is unique because of its speed (several microns per second) and its type (sliding and not crawling). It is powered by an actin/myosin motor under the membrane. The parasite’s entry follows the formation of a “tight junction” between the membrane of the parasite and the host cell’s one which ties the cytoskeleton of the two cells and acts as traction point for the motor. In the last years, Ménard and his group identified crucial components of both the motor and the entry junction of the parasite.
3/ The third axis of his research is to address protective bases against the parasite pre-erythrocytic phases and to identify new vaccinal candidates. Living parasites not developping in the liver and do not cause an erythrocytic infection constitute today the most efficient vaccine against the pre-erythrocytic phase of the disease. Using a combination of genetic tools, allowing to create attenuated parasites at different stages of the infection or of their development, and imaging techniques to in vivo analyze the fate of vaccinating parasites, Ménard and his team are trying to identify the most protective parasitic stages and their corresponding antigens
Impact
Robert Ménard’s work is providing valuable insights to better fight malaria, and his research is paving the way for the development of a vaccine against a disease killing up to a million person each year worldwide.
