Antibodies against the Plasmodium falciparum receptor binding domain of EBA-175 block invasion pathways that do not involve sialic acids

The 175-kDa Plasmodium falciparum erythrocyte binding protein (EBA-175) bin ds to its receptor, sialic acids on glycophorin A. The binding region withi n EBA-175 is a cysteine-rich region identified as region II. Antibodies aga inst region II block the binding of native EBA-175 to erythrocytes. We iden tified a P. falciparum strain, FVO, that could not invade erythrocytes devo id of sialic acids due to prior neuraminidase treatment, and in addition, s e used a strain, 3D7, that could invade such sialic acid-depleted erythrocy tes. We used these two strains to study the capacity of anti-region II anti bodies to inhibit FVO and 3D7 parasite development in vitro. Analysis of gr owth-inhibitory effects of purified FVO anti-region II immunoglobulin G (Ig G) with the FVO and 3D7 strains resulted in similar levels of growth inhibi tion. FVO and 3D7 strains were inhibited between 28 and 56% compared to con trol IgG. There appeared to be no intracellular grow,th retardation or kill ing of either isolate, suggesting that invasion was indeed inhibited. Incub ation of recombinant region II with anti-region II Ige reversed the growth inhibition. These results suggest that antibodies against region II can als o Interfere with merozoite invasion pathways that do not involve sialic aci ds. The fact that EBA-175 has such a universal and yet susceptible role in erythrocyte invasion clearly supports its inclusion in a multivalent malari a vaccine.