The surface variant antigens of Plasmodium falciparum contain cross-reactive epitopes

Plasmodium falciparum parasites evade the host immune system by clonal expr ession of the variant antigen, P. falciparum erythrocyte membrane protein 1 (PfEMP1). Antibodies to PfEMP1 correlate with development of clinical immu nity but are predominantly variant-specific. To overcome this major limitat ion for vaccine development, we set out to identify cross-reactive epitopes on the surface of parasitized erythrocytes (PEs). We prepared mAbs to the cysteine-rich interdomain region 1 (CIDR1) of PfEMP1 that is functionally c onserved for binding to CD36. Two mAbs, targeting different regions of CIDR 1, reacted with multiple P. falciparum strains expressing variant PfEMP1s. One of these mAbs, mAb 6A2-B1, recognized nine of 10 strains tested, failin g to react with only one strain that does not bind CD36. Flow cytometry wit h Chinese hamster ovary cells expressing variant CIDR1s demonstrated that b oth mAbs recognized the CIDR1 of various CD36-binding PfEMP1s and are truly cross-reactive. The demonstration of cross-reactive epitopes on the PE sur face provides further credence for development of effective vaccines agains t the variant antigen on the surface of P. falciparum-infected erythrocytes .