The role of Plasmodium falciparum variant surface antigens in protective immunity and vaccine development

Abstract

There is substantial immuno-epidemiological evidence that the parasite-encoded, so-called variant surface antigens (VSAs) such as PfEMP1 on the surface of infected erythrocytes (IEs) are important – in some cases probably decisive – determinants of clinical outcome of P. falciparum malaria. The evidence is increasingly being underpinned by specific molecular understanding of the pathogenic processes involved. Pregnancy-associated malaria (PAM) caused by placenta-sequestering IEs expressing the PfEMP1 variant VAR2CSA is a particularly striking example of this. These findings have raised hopes that development of PfEMP1-based vaccines to protect specifically against severe malaria syndromes – in particular PAM – is feasible. This review summarizes the evidence that VSAs are important targets of NAI, discusses why VSA-based vaccines might be feasible despite the extensive intra- and interclonal variation of VSAs, and how vaccines based on this type of antigens fit into the current global strategy to reduce, eliminate, and eventually eradicate the burden of malaria.