Immunity to and pathogenesis of Malaria
Plasmodium falciparum infected erythrocytes express on their surface, members of a diverse family of parasite molecules called PfEMP1 that are encoded by a family of 60 var genes in every parasite genome. These molecules interact with the surface of host cells and mediate parasite sequestration in tissues including the brain, an important step in the pathogenesis of severe cerebral malaria. In sub-Saharan Africa, though P. falciparum infection occurs throughout life, severe malarial disease tends only to occur in childhood. This could be explained if PfEMP1 variants differ in their ability to support the development of severe malaria and respond to naturally acquired antibodies. Although naturally acquired antibodies to PfEMP1 provide specific protection against the molecular variants that they recognise, PfEMP1 are often considered too diverse to be vaccine candidates. However, we and others have shown that parasites infecting children with severe malaria tend to express serotypes that are more broadly recognised suggesting that their antigenic diversity may be restricted. By sequencing large numbers of short var sequence “tags” expressed in parasites from Kenya we have developed an approach to comparing expression levels of different PfEMP1 types in clinical infections from Kenyan children. My group aims to identify new targets of malaria intervention by identifying and characterizing subsets of PfEMP1 that are associated with infections of children with low levels of naturally acquired immunity.