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MALARIA: Obstacles and Opportunities
Mechanisms of Immunity
Antibodies Sera from animals immunized with gametocyte-rich blood develop antibodies that, when mixed with gametocytes before ingestion by mosquitoes, will inhibit parasite development and maturation to oocysts within the mosquito (Carter and Chen, 1976; Gwadz, 1976). Monoclonal antibodies directed against gamete and zygote antigens will also inhibit parasite development in mosquitoes via several mechanisms. Some monoclonal antibodies require serum complement and act before fertilization to lyse gametes (Quakyi et al., 1987). Other monoclonal antibodies are complement independent and act either before fertilization, inhibiting zygote formation (Rener et al., 1983; Vermeulen et al., 1985), or work after fertilization (Vermeulen et al., 1985), inhibiting zygote penetration through the peritrophic membrane (Sieber et al., 1991). It is theoretically possible that antibodies could also inhibit zygote-ookinete transformation, inhibit ookinete motility, or inhibit ookinete penetration at later stages of parasite development.
Cell-Mediated Immunity Administration of immune T lymphocytes can reduce the density of gametocytes in the blood of recipient animals and reduce the ability of mosquitoes to transmit parasites by 95 percent (Harte et al., 1985). Helper and suppressor T lymphocytes are presumably also important for modulating antibody production. There is no evidence that ingestion of immune T cells can inhibit parasite development in the mosquito.
Targets of Transmission-Blocking Immunity
The sexual stage of the parasite life cycle provides several potential targets for immunological attack. As with the asexual stages, parasite antigens on the surface of erythrocytes infected with sexual stages could be targeted. Most of the research on transmission-blocking vaccines has focused on the extracellular sexual stages (gametes, zygotes, and ookinetes) found in the mosquito, in part because it is easy to measure antibodies against them, by feeding mosquitoes on infected blood mixed with antibodies and looking for inhibition of parasite development within the mosquito.
A number of proteins on the surface of sexual stages of malaria parasites have been identified by using monoclonal antibodies that inhibit parasite development in mosquitoes (Carter et al., 1988). These antigens are generally named by the initials of the parasite species (e.g., Pf for P. falciparum), the letter “s” (for sexual), and the approximate molecular weight in kilodaltons of the protein (Kaslow et al., 1988). Pfs230, Pfs48/45, and Pfs40/10 are expressed predominantly by gametes. Pfs25 is expressed predominantly