Recent progress in the development of malaria vaccines: memorandum from a WHO meeting.

The sixth meeting of the Scientific Working Group on the Immunology of Malaria reviewed studies on the identification and analysis of malarial antigens of asexual blood stages and sexual stages (gametes, zygotes, ookinetes) that may be exploited as targets for vaccination. Several proteins have been identified on the surface of mature schizonts and free merozoites, some of which can be recognized by antibodies which block in vitro parasite growth. Immunization of rodents and monkeys with purified antigens from the parasite surface membrane has conferred substantial immunity against subsequent challenge. A new class of malarial antigens has been identified which bind specifically to glycophorin, the major erythrocyte glycoprotein; these antigens are on the merozoite surface and it is possible that they mediate attachment to erythrocytes. Antibodies against these proteins also block parasite growth in vitro. The Plasmodium falciparum S-antigens have been characterized biochemically and the genes for two of these proteins sequenced. Several antigens have been localized in the invasion process, and monoclonal antibodies against these proteins block in vitro growth. Malarial antigens on the surface of P. falciparum trophozoite and schizont-infected erythrocytes may be involved in the cytoadherence of infected erythrocytes to endothelial cells. Surface antigens on gametes and zygotes of P. gallinaceum and P. falciparum have been shown to be the targets of transmission-blocking immunity. Monoclonal antibodies specific for these antigens block fertilization in the mosquito midgut. Transmission of P. gallinaceum can also be blocked by an antibody that blocks development of zygotes into ookinetes. Studies on the transmission of P. yoelii have identified a gamete protein that immunizes mice against transmission to mosquitos.