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Infect. Immun., Aug 1997, 3017-3023, Vol 65, No. 8
Copyright © 1997, American Society for Microbiology

Complement-mediated lysis of Plasmodium falciparum gametes by malaria- immune human sera is associated with antibodies to the gamete surface antigen Pfs230

J Healer, D McGuinness, P Hopcroft, S Haley, R Carter and E Riley
Institute of Cell, Animal and Population Biology, Division of Biological Sciences, University of Edinburgh, Scotland, United Kingdom. Julie.healer@ed.ac.uk

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.

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