Transmission-Blocking Vaccines

The objective of this program is to develop a TBV that would eliminate the 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, as the effect 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: TBVs are likely to have their greatest impact in areas of relatively low or 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 nets and other trials show that the frequency of severe malaria is reduced when transmission is reduced, even though most children remain infected.

P25

P25 is synthesized after fertilization of gametes and are the dominant surface proteins of the free living parasites (ookinetes) in the mosquito midgut. Orthologs are found in all malarial parasites. These closely related proteins consist of 4 EGF-like domains. Antibodies to these kill parasites in the midgut through mechanisms that are not fully understood.

Pxs230 Antigens

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 in chickens with avian malaria and in monkeys with primate malaria show that infection, even with high levels of gametocytes, fails to naturally induce appreciable antibody to these proteins. However, vaccination induces antibody that is strongly boosted by natural infection..

For these reasons, these antigens have a high priority as vaccine candidates. However, no group has yet to succeed in developing a method of satisfactorily expressing these proteins in the native conformation.

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