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Plasmodium falciparum imposes an enormous burden upon the developing world, with 300 to 500 million cases and 1 to 2 million deaths per year (94).Despite extensive research efforts, development of parasite drug resistance is a growing problem, and an effective vaccine is still lacking.Individuals living in areas of high P. falciparum transmission acquire protective immunity to severe malaria during early childhood after only a few symptomatic infections yet remain susceptible to uncomplicated disease and asymptomatic infection into adulthood (65).Thus, sterile immunity that prevents infection may never develop, but significant antidisease immunity is acquired relatively rapidly.While the protective targets of antidisease immunity are largely unknown, the parasite variant antigens exposed at the erythrocyte surface are considered strong candidates.Key virulence factors and prime candidates for antidisease vaccines have been identified in a family of clonally variant surface antigens collectively termed P. falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by about 60 var genes per haploid genome (9,40,92,97).P. falciparum-infected erythrocytes (IEs) bind host endothelium and other host cells, in turn sequestering infected cells away from the spleen, which would otherwise destroy them.Switching of var gene expression allows the parasite to modify the antigenic and functional properties of IEs, thereby evading immunity and affecting infection outcome.How antidisease immunity could be achieved rapidly against variant surface antigens is a deep mystery.Unraveling the basis for this protection represents a promising direction for antidisease malaria vaccines.This review considers how var gene organization may shape the functional and antigenic properties of PfEMP1 variants and regulate their expression during infection.
Kyes et al. (Sat,) studied this question.