CONCISE COMMUNICATION In Vivo Switching between Variant Surface Antigens in Human Plasmodium falciparum Infection

A semi-immune individual was retrospectively found to have maintained an apparently monoclonal and genotypically stable asymptomatic infection for months after clinical cure of a Plasmodium falciparum malaria episode. Before the attack, the individual had no anti-bodies to variant surface antigens (VSAs) expressed by an isolate (isolate A) obtained at the time of the episode or by a genotypically identical isolate (isolate B) obtained from the same individual 3 months later. Six weeks after the attack, a strong isolate A–specific VSA antibody response had developed in the complete absence of isolate B–specific antibodies. In contrast, plasma obtained 7 months after the attack contained high levels of VSA antibodies recognizing both isolates. This is the first direct evidence of in vivo switching between VSAs in human P. falciparum infection. Our results suggest that VSA switching is an important survival strategy of P. falciparum, enabling the parasite to persist despite protective, parasite-specific immune responses. Individuals living in areas of endemic Plasmodium falciparum transmission gradually acquire protective immunity against ma-laria. The targets and mechanisms of this protection are not fully understood, but an increasing body of evidence indicates that antibodies directed against parasite-encoded variant sur-face antigens (VSAs) on the surface of infected red blood cells (iRBCs) play an important role [1–3]. P. falciparum erythrocyte membrane protein 1 (PfEMP1) is the dominant and best char-acterized VSA. These highly polymorphic proteins are encoded by the var gene family, which is present at 40–50 loci per genom