B1 Immune profiling in Plasmodium sporozoite infections (Mueller/Matuschewski)
|Research Group:||Parasitology Unit|
|Address:||Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin-Mitte|
|Supervisor:||Dr. Katja Mueller / Professor Dr. Kai Matuschewski|
|Doctoral Researcher:||Oriana Kreutzfeld|
Pathogen stage conversion is a hallmark of parasites in general and permits unprecedented vaccine strategies. In the case of malaria, experimental immunizations with arrested liver stages has proven safe and efficacious against challenge infections in mice, primates, and humans. However, the molecular tracks of immune recognition and the immune effector mechanisms against Plasmodium pre-erythrocytic stages remain largely unsolved. While superior immunity can be achieved by a developmental arrest at liver-to-blood stage conversion, prognostic immune correlates remain to be identified. Preclinical assessment of correlates of protection in immunization and challenge studies with murine Plasmodium species can identify signatures of immune memory.We have previously established experimental malaria vaccine models, compared vaccine efficacy, and identified targets of CD8+ T cell responses against Plasmodium berghei liver stages by genome-wide epitope profiling.
In this project, the student will perform pre-clinical immunization and challenge studies to capture pathogen-specific host responses. Together we will establish different vaccine cohorts that either elicit lasting protection or are non-protective. Comparative immune profiling of the cohorts will be done prior and after challenge infections in organs and peripheral blood. Candidate signatures of protection will be validated by experimental genetics in the murine malaria model and cell-type specific mouse mutants.
We anticipate that systematic comparative immune profiling can inform ongoing human vaccine trials and boost malaria vaccine development.