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MALARIA: Obstacles and Opportunities
quito midgut extracts (Alger and Cabrera, 1972). Another mosquito, Aedes aegypti, when fed on rabbits immunized with whole Ae. aegypti extracts, suffered reduced reproductive capability (Sutherland and Ewen, 1974). Further work with Ae. aegypti fed on mice or rabbits immunized with selected mosquito body-part extracts demonstrated reduced viability of first generation offspring (Ramasamy et al., 1988) and increased mortality associated with the level and specificity of antibodies ingested (Hatfield, 1988a). Antibodies retained their immunological properties for two to three days and bound to the mosquito midgut epithelium (Hatfield, 1988b). Ramasamy and Ramasamy (1989) and Ramasamy et al. (1990) reported significant reductions in susceptibility to Ross River virus and Murray Valley encephalomyelitis virus in Ae. aegypti previously fed on rabbit blood-virus mixtures containing high levels of antibody against mosquito midgut extracts.
Recent work utilizing An. farauti (a vector of human malaria) and P. berghei (a rodent malaria parasite) showed that antibodies from mice immunized against mosquito midgut antigens appeared to prevent parasite ookinetes from penetrating the midgut of engorged mosquitoes (Ramasamy and Ramasamy, 1990). Interestingly, these same antibodies also reduced mosquito mortality rates, an undesirable outcome.
Although studies of antimosquito vaccines have used anthropophilic mosquitoes in unnatural animal host systems, they nevertheless hold promise for a new approach to reducing parasite transmission. This work is, however, in its early stages, and the opposing results obtained by Ramasamy and Ramasamy (1990) suggest that the immunological interactions among mosquitoes, host antibodies, and parasites are more complex than previously thought.
Identification of Mechanisms and Targets of Protective Immunity
Protective immunity can be induced in humans or experimental animals by repeated natural infection, by passive transfer of immune serum or cells, by immunization with radiation-attenuated parasites, or by immunization with subunit vaccines prepared by using purified parasite fractions, synthetic peptides or recombinant proteins. Identifying the mechanisms of such protective immunity will facilitate the development of subunit vaccines. Research on animal model systems will continue to be critical to the growth of basic knowledge in this area.
RESEARCH FOCUS: Continued use of animal model systems to identify and characterize mechanisms of protective antimalarial immunity.