Immune Responses - Project C3

Understanding the basis of strain specific protection against malaria.

Host lab: Ian Cockburn (ANU), Francis Ndungu (KEMRI) & Kathrin de la Rosa (Max Delbrück

Center)

 

Partner Lab: Leif Sander (HUB, Charité)

 

Controlled human malaria infection via sporozoite challenge with defined strains on parasites fails in around 1/3 individuals in endemic areas. It has been hypothesized that this is due to liver stage immunity, however no evidence has been found of naturally occurring liver stage immunity numerous previous studies. We hypothesise instead, that protection is mediated by antibodies that target the variant surface antigens expressed by first blood stage parasites emerging from the liver. This is based on previous work that suggests that the var genes that encode variant surface antigens epigentically reset after passage through the mosquito. To test this hypothesis we will

isolate sera and generate monoclonal antibodies specific for PfEMP1 from individuals in Kilifi, Kenya who did not develop malaria infection and screen them for reactivity with those var genes known to emerge first after infection. We will examine how strain specific these antibodies are and determine their ability to prevent adhesion and induce parasite clearance. The ultimate aim of this project is to identify a panel of highly cross reactive var genes capable of neutralizing multiple strains of parasites rapidly by targeting the first parasites to emerge from the liver.