Identifying targets and mechanisms of acquired immunity to severe malaria in children

Summary This project aims to identify immune responses that protect against severe malaria in young children. It will involve testing samples from young children in specific immunologic assays

Project Details

Malaria caused by Plasmodium falciparum is a leading cause of mortality and morbidity globally, particularly among young children. After repeated exposure, individuals develop effective immunity that controls blood-stage parasitaemia, thereby reducing clinical symptoms and life-threatening complications. Antibodies are important mediators of this acquired immunity. The demonstration that naturally acquired antibodies are associated with protection from malaria is one of the criteria used to objectively prioritize malaria antigens for malaria vaccine development.

We have recently completed a case-control study of severe malaria in children living on the North coast of Papua New Guinea. Cases were identified at Madang hospital and were defined as having severe malaria according to the World Health Organization criteria. Each case of severe malaria was matched to a healthy community control. Blood samples were taken from cases at the time of hospital admission and when the patient had recovered. For controls, samples were taken at the time of enrolment into the study.

The project will determine levels of antibodies to a range of malaria antigens, and specific epitopes by Enzyme-linked immunosorbent assay (ELISA) and flow cytometry, and evaluating functional antibody activity, including direct neutralization, complement activation, and opsonic phagocytosis. The levels of these antibodies and functional activities will then be related to clinical outcome using statistical analysis including regression techniques.

These findings will help us understand how immunity contributes to protection from severe malarial disease progression. The findings are valuable for advancing vaccine development by providing evidence supporting certain malaria antigens as targets of protective immunity.