Non-var-Encoded Variant Antigen Families in Plasmodium falciparum as Targets for Naturally Acquired Immunity to malaria. (360G-Wellcome-084378_B_07_A)

The Plasmodium falciparum genome contains large multigene families that code for hypervariable antigens, which are exported to the surface of the infected host erythrocyte and represent targets of naturally acquired immunity to malaria. These variant surface antigens (VSA) act at the host-parasite interface, ensuring parasite survival without inducing a sterilizing host immune response. With the exception of the well-demonstrated roles of var-encoded P. falciparum erythrocyte membrane protein (PfEMP)1 in virulence and immune evasion, the biological significance of other VSA and their role in the acquisition of antimalarial immunity in endemic regions is largely unknown. Here we propose to determine whether two other VSA, RIFINs and STEVORs, encoded by the rif and stevor multigene families respectively, are targets of natural immunity and whether the hypervariable regions of these structurally-related proteins are exposed to antibody-mediated immune selection at the erythrocyte surface. We will define the expression patterns and measure the naturally acquired antibody responses to these antigens in wild isolates of P. falciparum from coastal Kenya. By identifying and characterising the molecular targets of naturally acquired immunity, this research will advance current understandings of P. falciparum antigenic variation and the mechanisms of natural acquisition of protective immunity against malaria.