A monoclonal antibody capable of blocking the binding of Pf200 (MSA-1) to human erythrocytes and inhibiting the invasion of Plasmodium falciparum merozoites into human erythrocytes.

Abstract

Glycophorin A is a major receptor on human erythrocytes for Plasmodium falciparum, the human malaria parasite. In this work, we have produced four glycophorin A-specific mAb: 2B10, 1E4, 3H12, and 3H2. 2B10 was mapped to the amino terminal region of glycophorin (amino acids 1-31), and its binding to erythrocytes was fully dependent on sialic acid residues. 3H2 bound to the region close to the cell membrane, and its binding to Wr (b-) erythrocytes was significantly decreased, compared with its binding to Wr (b+) erythrocytes. 1E4 and 3H12 recognized sites between those identified by 2B10 and 3H2. Pf200 (MSA-1) is a surface protein on the P. falciparum merozoite which has been shown to bind to erythrocytes. By reciprocal inhibition assays, 2B10 and MSA-1 could be shown to share the same determinant on erythrocytes. Using an in vitro assay, we have shown that 2B10 was the most efficient inhibitor of the invasion of human erythrocytes by P. falciparum merozoites. We conclude that the binding site for MSA-1 is primarily located on the amino terminal region, amino acids 1-31, of glycophorin A, and that 2B10 is valuable for additional study of the interactions between P. falciparum merozoites and human erythrocytes.

A multifunctional serine protease primes the malaria parasite for red blood cell invasion

“…MSP1 is synthesized as an B195-kDa glycosyl phosphatidylinositol-anchored precursor that assembles as a complex with two peripheral membrane proteins called MSP6 and MSP7 (Holder et al, 1985;Stafford et al, 1996;Pachebat et al, 2001;Trucco et al, 2001;Kauth et al, 2003Kauth et al, , 2006. The MSP1/ 6/7 complex is abundant, uniformly coats the merozoite surface and is involved in the receptor-mediated interactions that initiate erythrocyte invasion (Su et al, 1993;Goel et al, 2003;Li et al, 2004). Just prior to egress, all three MSPs undergo a series of precise 'primary' proteolytic cleavage events (Freeman and Holder, 1983;Lyon et al, 1986Lyon et al, , 1987Holder et al, 1987;McBride and Heidrich, 1987;Stafford et al, 1994;Pachebat et al, 2007).…”