Research Fellows Directory
Dr Julius Hafalla
London School of Hygiene and Tropical Medicine
Malaria is responsible for an estimated 250 million episodes of clinical disease and 600,00 to 1.2 million deaths each year . Despite recent reductions in the burden of malaria in some endemic areas, sustained control, elimination or eradication of the disease will require a highly efficacious vaccine that prevents malaria transmission as well as reducing the burden of disease. Vaccination against malaria is feasible, as demonstrated with radiation-attenuated sporozoite vaccine, which protects experimental animals and humans by targeting the clinically silent liver stages. Potent protection largely depends on CD8+ T cells, a type of white blood cell that is tailor-made to kill obligate intracellular pathogens. Malaria-infected cells display fragments of parasite proteins, which are then recognised and targeted by CD8+ T cells. How CD8+ T cells are activated following immunisation and how they execute protective functions are key considerations for vaccination. However, characterisation of CD8+ T cells is hampered by the lack of identified malaria protein targets. Of concern, the circumsporozoite protein, which is the basis of the most advanced malaria vaccine candidate (RTS,S), is not an essential target of CD8+ T cells induced by attenuated sporozoites in several mouse strains. We have made considerable advances by identifying for the first time, fragments of malaria proteins that are targeted by CD8+ T cells generated by vaccination in a relevant mouse strain C57BL/6. Notably, CD8+ T cells against one of the target proteins elicit partial protection against infection. Our work exemplifies how immunisation by complex pathogens can be dissected to identify targets of immune responses. The principal impact of our research is on both basic immunology using malaria as an infection model, and translational research into malaria vaccine development.
The outcome of our work has obvious relevance for vaccine development.
Interests and expertise (Subject groups)