Immune responses

Pathogen defence is a critical determinant in host-parasite coevolution and survival of an infected individual. In humans, naturally acquired immunity against Plasmodium infections develops very gradually over the course of the entire childhood and only after several clinical episodes, but remains incomplete, and wanes rapidly after migration out of endemic areas. A better cellular and molecular understanding of both the individual contributions and the interplay of innate and 10 adaptive defence mechanisms in anti-malaria immunity remains a research priority and has important translational implications, ranging from identification of high-risk patients to evidencebased malaria vaccine development. In this research area, three projects will uncover longstanding questions in immunity to malaria parasites.


Projects


Dissecting innate immune responses to plasmodia and their impact on disease and vaccination

LEIF ERIK SANDER (Charité) in partnership with Ian Cockburn (ANU)

The project will achieve the first systematic analysis of pattern recognition of viable humaninfecting Plasmodium parasites. Against the background of an abundance of conflicting data of innate sensing in murine models, a careful assessment of human innate responses to Plasmodium infection is particularly desirable. Candidate viability and pathogen-associated molecular patterns will be tested in transgenic sporozoite murine infection models for their potential to enhance live attenuated malaria vaccine strategies.

Identification and analysis of platelet polymorphisms associated with malaria susceptibility

BRENDAN MCMORRAN (ANU) in partnership with Frank Mockenhaupt (Charité)

In the project the seminal finding that platelets are instrumental in killing of Plasmodium-infected erythrocytes permits the functional testing of whether candidate polymorphisms in platelet-associated genes cause malaria susceptibility. This study encompasses genotyping in patient cohorts and cell culture assays as proxy for platelet functions in infected patients. Sporozoite-based immunization strategies are presently one of the most promising roads towards an efficacious malaria vaccine.

Novel adjuvants for pre-erythrocytic stage vaccines

IAN COCKBURN (ANU) in partnership with Leif Erik Sander (Charité)

The project will combine self-devised immunoglobulin transgenic mice and lentiviral knockdown libraries for the evidence-based development of adjuvants that permit superior B cell responses against inactivated sporozoites, which are notoriously weak in eliciting lasting immunity. Hence, this project could remove a major roadblock in development of whole sporozoite vaccines for use in endemic countries.