Poster Presentation First Malaria World Congress 2018

In vivo mechanisms of antibody-mediated parasite control during blood-stage Plasmodium infection in mouse models (#407)

Jasmin Akter 1 , David Khoury 2 , Rosemary Aogo 2 , Ismail Sebina 1 , Trish Elliott 1 , Bryce S. Thomas 1 , Lily G.Fogg 1 , Deborah Cromer 2 , Megan Soon 1 , Arya SheelaNair 1 , Lianne Lansink 1 , Jessica Engel 1 , Kylie R. James 1 , Miles P. Davenport 2 , Ashraful Haque 1
  1. Malaria Immunology Laboratory,, QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia
  2. Infection Analytics Program, Kirby Institute, The University of New South Wales, Kensington, NSW 2052, Australia

Plasmodium-specific antibodies play an important role in immunity to malaria. However, mechanisms of action for these antibodies remain unclear in vivo. Here, using two murine models of blood-stage malaria, P. yoelii 17XNL and P. chabaudi chabaudi AS infection, we studied how parasite-specific antibodies in immune serum controlled malaria parasites in vivo. We used an RBC adoptive transfer approach involving the injection of fluorescently-labelled parasitised RBCs (pRBCs) into recipient mice treated with immune or non-immune sera. This enabled us to track (i) parasites developing within and rupturing out of transferred first generation (Gen0) pRBCs, and (ii) the subsequent growth of parasites in newly invaded, unlabelled recipient (Gen1+) RBCs. Our data revealed that antibodies did not accelerate clearance of Gen0 pRBCs, despite being highly effective at controlling total parasitemia. Instead, parasite-specific antibodies prevented Plasmodium from parasitizing the next generation (Gen1+) of RBC. By using clodronate liposome treatment, we revealed that phagocytes contributed to optimal antibody function in vivo, while complement-mediated direct killing played no role. Finally, we found that parasite-specific IgG bound weakly to the surface of pRBC, but nevertheless exhibited strong recognition of structures, particularly present in schizonts, which we postulate to be merozoites. Thus, in two mouse models of robust antibody-mediated immunity to blood-stage infection, antibodies do not bind well to pRBC nor accelerate their clearance. Instead we propose that antibodies targeted merozoites partially for phagocyte-dependent control, but not complement-dependent direct killing. Our data in experimental models suggest that naturally-acquired antibodies, which are protective against high blood-stage parasite densities, need not target pRBC if merozoite targeting is effective.