The objective of this program is to develop a transmission-blocking vaccine (TBV) that would eliminate malaria transmission in low-endemic areas and reduce disease burden in moderate- and high-transmission areas. Unlike asexual blood-stage antigens that are primarily designed as anti-disease vaccines, TBVs prevent transmission by blocking infection of mosquitoes with antibodies taken up in the blood meal.
Conceptually, the use of these vaccines will parallel conventional malaria control programs, such as residual insecticide spraying and insecticide-treated bed nets. TBVs are likely to have similar broad strengths and weaknesses: They are likely to have their greatest impact in areas of relatively low epidemic transmission but are unlikely to reduce the prevalence of parasitized humans in areas of high transmission. However, even in areas of high transmission, data from insecticide-treated bed net trials and other trials show that the frequency of severe malaria is reduced when transmission is reduced, even if most children remain infected.
P25 is synthesized after fertilization of gametes and is composed of the dominant surface proteins of the free living parasites (ookinetes) in the mosquito midgut. Orthologs, found in all malarial parasites, are closely related proteins consisting of 4 EGF-like domains. Antibodies to these orthologs kill parasites in the midgut through mechanisms that are not fully understood.
These proteins are expressed in gametocytes and exposed on the surface of gametes following their release from the red cell after ingestion by the mosquito. Gene knockout experiments show that these proteins are critical to fertilization of the released gametes. Monoclonal antibodies against these proteins, especially in the presence of complement, are highly effective in killing parasites. Experiments with avian malaria in chickens and with primate malaria in monkeys show that natural infection, even with high levels of gametocytes, fails to induce appreciable antibodies to these proteins. However, vaccination induces antibodies that are boosted by natural infection.
These antigens have high priority as vaccine candidates. However, no group has yet succeeded in developing a method of satisfactorily expressing these proteins in their native conformation.
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Last Updated November 17, 2008