(3.) Malaria pathogenesis and vaccination approaches

Parasite dynamics and Malaria pathogenesis

Malaria is one of the most serious tropical diseases with an estimated 210 million cases and ~660,000 deaths in 2010. Some strains of malarial parasites are known to cause more serious disease outcomes than other strains, i.e., leading to cerebral malaria and death. Thereby, parasite specificity for particular red blood cells (RBC) seems to play a key role in disease development. In this joined project with the group of Ann-Kristin Mueller from the University Hospital Heidelberg, we developed a mathematical model for blood stage malaria infection and immune dynamics, thereby accounting for RBC age structure and disease induced anaemia. Combining the model with experimental data of different murine malaria strains, we aim at providing a systematic and quantitative analysis of how parasite specificity for RBC influences the spread of infection and disease development. The results are an important prerequisite for determining the precise mechanisms that lead to the observed neuropathology within the brain during malaria infection.

The project is funded by the FRONTIER-initiative and the MWK Baden-W├╝rttemberg, RiSC-initiative.

  • Thakre N*, Fernandes P*, Mueller AK, Graw F: Examining the reticulocyte preference of two Plasmodium berghei strains during blood-stage malaria infection. Front Microbiol 2018, 9:166. doi: 10.3389/fmicb.2018.00166 (*these authors contributed equally)

 

Optimising vaccination regimens agains Malaria infection

In a second joined project with the group of Ann-Kristin Mueller, we aim to determine optimal malaria vaccination regimens that rely on the use of attenuated parasites. Based on data showing the influence of varying dosage, timing and frequencies during prime-boost vaccination regimes in mice, we use mathematical models to describe and quantify the dynamics of memory T cell generation in various organs. Thereby, we could reveal the interplay and importance of organ-specific T cell responses for the generation of protective, tissue-resident T cells in the liver.

This project is also funded by the FRONTIER-initiative and the MWK Baden-W├╝rttemberg, RiSC-initiative.

  • Frank R, Gabel M, Heiss K, Mueller AK, Graw F: Varying immunizations with Plasmodium radiation-attenuated sporozoites alter tissue-specific CD8+ T cell dynamics. Front Immunol 2018, 9:1137. doi: 10.3389/fimmu.2018.01137
Contact: E-Mail (Last update: 11/06/2018)