Plasmodium P25 and P28 Surface Proteins: Potential Transmission-Blocking Vaccines

Malaria arises from the infection of red blood cells by protozoan parasites of the genus Plasmodium that are transmitted by anopheline mosquitoes. More than 400 species of Anopheles mosquitoes are known, of which about 40 species are characterized as important disease vectors for human malaria transmission (29). It is estimated that 300 to 500 million cases of malaria and over 1 million deaths from the disease occur each year (49). The Plasmodium parasite must complete its development in the mosquito before it can be transmitted to the vertebrate host and cause malaria. Each stage of parasite development in the mosquito offers potential targets to interfere with malaria transmission. Development of the malaria parasite in the mosquito begins when the gametocyte forms of the parasite are picked up by the mosquito in the blood meal from an infected human and quickly develop into extracellular gametes in the mosquito midgut. After fertilization, round zygotes form and transform into banana-shaped ookinetes. The ookinetes are motile and must exit the gut by crossing the peritrophic membrane and midgut epithelium. On the basal side of the epithelium, surviving ookinetes lodge against the basal lamina and transform into spherical oocysts. In the oocyst, the parasite develops into several thousand sporozoites, which then exit the oocyst and are carried by the hemolymph to the mosquito’s salivary glands to infect another host (22). There is ongoing research to develop antiparasite vaccines against each stage of the complicated life cycle of Plasmodium (17, 24). Liver-stage vaccines are intended to reduce infection rates, and asexual-blood-stage vaccines will reduce disease severity and the risk of death during infection. Transmissionblocking vaccines would prevent the spread of disease by targeting antigens expressed in the mosquito stage on the surfaces of the gametocyte, gamete, zygote, and ookinete forms of the parasite (6, 61). These vaccines induce antibodies in the human host that inhibit parasite development in the mosquito midgut and thereby block parasite transmission to another person. This article reviews the biology and structural knowledge of the Plasmodium P25 and P28 proteins and their contributions to transmission-blocking vaccine development.