Anti-gamete monoclonal antibodies synergistically block transmission of malaria by preventing fertilization in the mosquito

Abstract

Experiments from our laboratory previously demonstrated that infected chickens immunized with gametes of the avian malaria parasite Plasmodium gallinaceum were no longer infectious to the mosquito vector Aedes aegypti and that this transmission-blocking immunity was mediated by antibody. To identify those antigens that are the targets of transmission-blocking immunity, hybrid mouse cell lines secreting monospecific antibodies to surface antigens on male and female gametes of P. gallinaceum have been produced. We describe two such anti-gamete antibodies, 10G3 and 11C7, which act synergistically both to agglutinate male gametes in vitro and to suppress infectivity of parasitized blood fed to mosquitoes. In the presence of a mixture of these antibodies, the male gametes became agglutinated during gametogenesis and failed to detach from the residual body of the gametocyte. In the presence of either antibody alone, the male gametes readily detached during gametogenesis. Neither antibody alone mediated more than a slight reduction in infectivity of gametocytes to mosquitoes. Although both 10G3 and 11C7 recognize surface antigens on both male and female gametes, agglutination and prevention of detachment of the male gametes from the residual body appears to be the primary mechanism by which the mixture of these antibodies prevents fertilization.