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Title: Mechanisms of naturally acquired transmission-blocking immunity to Plasmodium falciparum malaria
Author: Healer, Julie
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1998
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Monoclonal antibodies to the gamete surface antigens of Plasmodium falciparum, 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 P. falciparum. By immunoprecipitation, it was 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 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 P. falciparum gametocytes to Anopheles 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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available