Malaria vaccine(Pevion Biotech AG)

Malaria is a highly prevalent disease caused by infection by Plasmodium spp., which infect hepatocytes and erythrocytes. Blood-stage infections cause devastating symptoms and can persist for years. Antibodies and CD4(+) T cells are thought to protect against blood-stage infections. However, there has been considerable difficulty in developing an efficacious malaria vaccine, highlighting our incomplete understanding of immunity against this disease. Here, we used an experimental rodent malaria model to show that PD-1 mediates up to a 95% reduction in numbers and functional capacity of parasite-specific CD8(+) T cells. Furthermore, in contrast to widely held views, parasite-specific CD8(+) T cells are required to control both acute and chronic blood-stage disease even when parasite-specific antibodies and CD4(+) T cells are present. Our findings provide a molecular explanation for chronic malaria that will be relevant to future malaria-vaccine design and may need consideration when vaccine development for other infections is problematic.

Development of new medicines for malaria is a challenging and important topic of applied research because malarial parasites rapidly adapt to man-made interventions. Best studied examples are widely used drugs such as chloroquine, sulfadoxin-pyrimethamine (SP), and, recently, artemisinins; all of them can lose efficacy after large-scale introduction. In addition to drugs, malaria vaccines re-emerged on the agenda of funding bodies and research institutions after a period of quietness and desperation. This time the communities' aims are high: a registered and effective malaria-vaccine. So far, only one candidate shows modest efficacy, a quantum leap in malaria vaccine research, whereas others have not met the high expectations. In this overview, I will summarize basic thoughts and principles behind our work and illustrate them with examples of current projects of my group.