title: Complement-mediated lysis of Plasmodium falciparum gametes by malaria-immune human sera is associated with antibodies to the gamete surface antigen Pfs230.
abstract: Antibodies to the sexual-stage surface antigens of Plasmodium falciparum, Pfs230 and Pfs48/45, can abolish the infectivity of gametes to mosquitoes; 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 distinct 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 recognition of Pfs230 and Pfs48/45 is limited, despite universal exposure to P. falciparum gametocytes. In vitro complement-mediated lysis of P. falciparum gametes was positively associated with the presence of antibodies to Pfs230 but not with antibodies to the N-terminal region of the precursor molecule (Pfs260), which is shed from the gametocyte surface at the time of gametogenesis. Similarly, antibodies to two other gametocyte-specific proteins, Pfs48/45 and Pfg27/25, were not associated with gamete lysis. All sera which mediate gamete lysis contain immunoglobulin G1 (IgG1) and/or IgG3 antibodies to gamete surface proteins as determined by an enzyme-linked immunosorbent assay. These data suggest that Pfs230 is a major target of complement-fixing antibodies which may be important for antibody-mediated transmission-blocking immunity.
authors.affiliation: Institute of Cell, Animal and Population Biology, Division of Biological Sciences, University of Edinburgh, Scotland, United Kingdom. Julie.healer@ed.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Healer
authors.forename: D
authors.initials: D
authors.lastname: McGuinness
authors.forename: P
authors.initials: P
authors.lastname: Hopcroft
authors.forename: S
authors.initials: S
authors.lastname: Haley
authors.forename: R
authors.initials: R
authors.lastname: Carter
authors.forename: E
authors.initials: E
authors.lastname: Riley
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003165:Complement System Proteins / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007106:Immune Sera / Q000276:immunology*; D007074:Immunoglobulin G / Q000145:classification; D007223:Infant; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology*; D011233:Precipitin Tests
chemical_list: D000913:Antibodies, Protozoan; D007106:Immune Sera; D007074:Immunoglobulin G; D003165:Complement System Proteins