Properties of epitopes of Pfs 48/45, a target of transmission blocking monoclonal antibodies, on gametes of different isolates of Plasmodium falciparum

TLDR

The study investigates the epitope properties of the gamete surface protein Pfs 48/45, a target for malaria transmission‑blocking antibodies. A two‑site immunoradiometric assay identified three distinct, non‑repeated epitope regions on Pfs 48/45 peptides. Region I epitopes elicit monoclonal antibodies that potently suppress gametocyte infectivity to mosquitoes, whereas regions II and III alone are less effective but act synergistically when combined; a fourth epitope reacts only in reduced form but does not affect infectivity.

Abstract

Summary We have studied the properties of epitopes on Plasmodium falciparum gamete surface protein Pfs 48/45, a target antigen of malaria transmission blocking antibodies. Using a two site immunoradiometric assay we have defined three spacially separate, non‐repeated, epitope regions on the peptides representing this antigen. Epitope region I is a target of monoclonal antibodies (MoAbs) which strongly suppress infectivity of gametocytes of P. falciparum to mosquitoes; the effect is complement independent and is mediated as effectively by the monovalent Fab fragments as by intact MoAb. Epitope region II consists of two spacially close subregions, Ha and lib; variant forms of epitopes Ha and lib occurred in different isolates of P. falciparum. Epitope region III also showed slight structural modification between isolates. MoAbs against regions II or III were relatively ineffective in suppressing gametocyte infectivity compared to MoAbs against region I. However, certain combinations of MoAbs against regions II and III together acted synergistically to suppress infectivity to mosquitoes. All these epitopes failed to react with MoAb when the antigen was presented in reduced form. A fourth epitope, however, was identified which reacted strongly with MoAb when the antigen was presented in reduced form. The MoAb against this epitope had no effect on the infectivity of gametocytes of P. falciparum to mosquitoes.