Pf332 Repeat Sequences Inhibit Plasmodium Falciparum Growth In Vitro On Their Own And In Cooperation With Human Monocytes

Abstract

Repeat sequences from the Plasmodium falciparum blood stage antigen Pf332 frequently comprise the pentapeptide VTEEI, an epitope recognized by certain parasite neutralizing antibodies. This motif was assembled in octavalent multiple antigen peptides as trimers (VTEEI)3 (MAP1). We optimized in vitro conditions for studying the inhibition of P. falciparum growth with rabbit antibodies raised against MAP1. When total IgG was used, the parasite growth inhibitory effect was unexpectedly low and agglutination of the erythrocytes in the culture was observed in the microscope, indicating that the low inhibition obtained was due to presence of haemagglutinins. Haemagglutinins bind both infected and non infected red blood cells. When parasitised erythrocytes rupture, released merozoites infect non infected red blood cells. When haemagglutinins were removed by absorbtion the inhibitory capacity of IgG was considerably increased. Affinity purified Pf332 specific antibodies induced higher inhibition at lower levels than did the rabbit total IgG. We also found that MAP1-specific antibodies increased the capacity of monocytes to inhibit growth of parasites. Surface exposure of Pf332 makes it accessible to opsonic??ic antibodies involved in phagocytosis of parasite infected erythrocytes and can mediate cellular killing of parasite. Thus, Pf332 specific antibodies proved able to inhibit parasite growth on their own as well as in cooperation with normal human monocytes.