Characterization of the modes of action of anti-Pbs21 malaria transmission-blocking immunity: ookinete to oocyst differentiationin vivo

Abstract

The impact of immune sera, and peripheral blood cells (PBC) from mice immunized with Plasmodium berghei ookinetes; and of purified immunoglobulin or Fab fragments from anti-Pbs21 monoclonal antibody 13.1, upon establishment of oocyst infections in the mosquito was studied. Infections were initiated either from gametocyte-infected mice, or membrane feeders which contained either gametocytes or mature ookinetes. PBC from ookinete-immunized mice presented with non-immune serum failed to show any transmission-blocking activity. Anti-ookinete serum, intact anti-Pbs21 monoclonal antibody 13.1 or its Fab fragments, all inhibited oocyst formation significantly. When gametocyte-infected mice or gametocytes in membrane feeds were used, inhibition did not directly correlate with antibody concentration. In membrane feeders that contained ookinetes and antibody, concentration-dependent inhibition usually occurred. The efficacy of purified 13.1 IgG was dependent upon the ookinete concentration. The ookinete plasmalemma and cytoplasm were significantly disturbed after 12 h in bloodmeals that contained antibody 13.1, but not in the isotype controls. These changes may have caused the observed failure of the ookinete to migrate as rapidly as the controls from the destructive environment of the bloodmeal.

Functional characterization of Plasmodium berghei PSOP25 during ookinete development and as a malaria transmission-blocking vaccine candidate

“…Previous studies have explored passive transfer of transmission blocking mAbs (e.g. Pbs21 mAb clone 13.1) for TB activities [31, 47]. In this study, an IgGl-type mAb against PSOP25 significantly inhibited the development of ookinetes and oocyst when administered through passive transfer prior to mosquito feeding, and the TB activities were comparable to those from the full-length rPSOP25 immunization group.…”

P25 and P28 proteins of the malaria ookinete surface have multiple and partially redundant functions

“…Anti‐P25/28 immunity attacks the parasite in the mosquito and is antibody mediated (Kaslow, 1998). A P28 monoclonal antibody (Mab) inhibited parasite development by three mechanisms (Ranawaka et al ., 1993, 1994a,b). First, zygotes/ookinetes were killed in the midgut by antibody‐dependent cell‐mediated killing; secondly, ookinetes were prevented from differentiating into oocysts partly as a consequence of the antibody preventing interaction of the ookinete with the midgut epithelium; and thirdly, the development of young oocysts was inhibited by IgG.…”

The Plasmodium berghei sexual stage antigen PSOP12 induces anti-malarial transmission blocking immunity both in vivo and in vitro

“…Both fertilization and ookinete formation within the midgut can be inhibited by the presence of vaccine-induced antibodies within the mosquito blood meal. Fertilization can be blocked through agglutination, steric hindrance, or complement-mediated lysis of gametes [5,6], whereas ookinete development can be inhibited or fully prevented by complement-mediated lysis, melanization, antibody-dependent phagocytosis or by blocking recognition of the midgut epithelial cells [7,8]. In the laboratory transmissionblocking antibodies can result in profound and often total reduction s in parasite transmission to the mosquito vector.…”