COMPLEMENT-MEDIATED LYSIS OF PLASMODIUM-FALCIPARUM GAMETES BY MALARIA-IMMUNE HUMAN SERA IS ASSOCIATED WITH ANTIBODIES TO THE GAMETE SURFACE-ANTIGEN PFS230

Antibodies to the sexual-stage surface antigens of Plasmodium falcipar um, Pfs230 and Pfs48/45, can abolish the infectivity of gametes to mos quitoes; these antigens have been proposed as candidates for inclusion in a malaria transmission-blocking vaccine. One possible mechanism of antibody-mediated transmission blocking is complement-mediated gamete lysis, We have used a panel of human sera from geographically distinc t regions where malaria is endemic to investigate whether this may be a mechanism of naturally acquired transmission-blocking immunity to P, falciparum. By immunoprecipitation, we have shown that antibody recog nition of Pfs230 and Pfs48/45 is limited, despite universal exposure t o P. falciparum gametocytes. In vitro complement-mediated lysis of P. falciparum, gametes was positively associated with the presence of ant ibodies to Pfs230 but not with antibodies to the N-terminal region of the precursor molecule (Pfs260), which is shed from the gametocyte sur face at the time of gametogenesis. Similarly, antibodies to two other gametocyte-specific proteins, Pfs48/45 and Pfg27/25, were not associat ed with gamete lysis, All sera which mediate gamete lysis contain immu noglobulin G1 (IgG1) and/or IgG3 antibodies to gamete surface proteins as determined by an enzyme-linked immunosorbent assay. These data sug gest that Pfs230 is a major target of complement-fixing antibodies whi ch may be important for antibody-mediated transmission-blocking immuni ty.