EPITOPE SPECIFICITY AND CAPACITY TO INHIBIT PARASITE GROWTH IN-VITRO OF HUMAN-ANTIBODIES TO REPEAT SEQUENCES OF THE PLASMODIUM-FALCIPARUM ANTIGEN-AG332

It has earlier been shown that the Plasmodium falciparum-reactive huma n monoclonal antibody 33G2 inhibits parasite growth in vitro as well a s cytoadherence of infected red blood cells to melanoma cells in vitro . MoAb 33G2 recognizes an epitope of the P. falciparum antigen Ag332 a nd cross-reactive determinants in Pf155/RESA and Pf11.1 located in rep etitive regions containing sequences of regularly spaced pairs of glut amic acid. To study whether antibodies of this specificity frequently occur in human immune sera and if they could be of importance for prot ective immunity, antibodies were affinity purified on MoAb 33G2 reacti ve Ag332 peptides. The epitope specificity of the affinity purified an tibodies, determined by the Pepscan method, resembled that of MoAb 33G 2, but showed differences in fine specificity. The antibodies cross-re acted to some extent with Pf11.1 and Pf155/RESA repeat peptides as det ected by peptide ELISA and Pepscan. In indirect immunofluorescence all purified antibodies displayed a dotted pattern of staining of late st age infected red blood cells of two lines of the P. falciparum strain FCR3, including a Pf155/RESA deficient line. The in vitro growth of th ese two lines was efficiently inhibited by the affinity purified antib odies, indicating that their inhibitory effect was mainly due to react ivity with antigens other than Pf155/RESA. This, and the fact that Pf1 1.1 has been shown not to be expressed by the asexual stages suggests that Ag332 may be an important target for potentially protective antib odies in vivo and that Ag332 based immunogens are of interest for deve lopment of malaria subunit vaccines.