Monoclonal antibodies to the gamete surface antigens of <I>Plasmodium falciparum, </I>Pfs230 and Pfs48/45, can abolish the infectivity of gametes to mosquitoes, hence 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. A cohort of human sera, from geographically distinct malaria-endemic regions, was used to investigate whether this may be a mechanism of naturally acquired transmission-blocking immunity to <I>P. falciparum. </I>By immunoprecipitation, it was shown that antibody recognition of Pfs230 and pfs48/45 is limited, despite universal exposure to <I>P. falciparum</I> gametocytes. <I>In vitro</I> complement-mediated lysis of <I>P. falciparum</I> 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 Pfs27/25 were not associated with gamete lysis. All sera which mediated gamete lysis contained IgG1 and/or IgG3 antibodies to gamete surface proteins as determined by ELISA. These data suggest that Pfs230 is a major target of complement-fixing antibodies which may be important for antibody-mediated transmission-blocking immunity. A selection of these malaria-immune human sera were tested for their ability to affect the infectivity of <I>P. falciparum</I> gametocytes to <I>Anopheles</I> mosquitoes. It was found that transmission-reducing effects of the sera were associated with the presence of IgGl antibodies to the gamete surface, specifically against the protein, Pfs230.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:652285 |
| Date | January 1998 |
| Creators | Healer, Julie |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/14038 |
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