Cross-Species Immunity in Malaria Vaccine Development: Two, Three, or Even Four for the Price of One?

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Abstract
For millennia, malaria has been one of the most deadly human infectious diseases in the world, and it is still the cause of about 2 million deaths per year, mainly among young children and pregnant women. Malaria is caused by protozoan parasites of the genus Plasmodium, four species of which are infectious for humans: Plasmodium falciparum (the most deadly species, responsible for 80% of infections worldwide and 90% of malaria-related deaths), Plasmodium vivax, Plasmodium malariae, and Plasmodium ovale (56). The "gold standard" for full and sterile immunity against malaria—immunization with Plasmodium whole-organism, radiation-attenuated sporozoites (RAS)—was described for mice, monkeys, and humans over three decades ago (12, 14, 45a). The original RAS immunization strategy, however, usually required either the bites of many irradiated mosqui- toes on multiple occasions or intravenous inoculation of sporozoites, both of which were considered impractical for mass vaccination campaigns (36, 45a). The advent of recom- binant DNA technology in the 1970s led many researchers to believe that the development of vaccines for the majority of known diseases, including malaria, was imminent (45). Although significant achievements in vaccinology have indeed been made using this technology (e.g., the pertussis vaccine (47)), the quest for a malaria vaccine remains unfulfilled. Sev- eral potential candidate vaccines have progressed to clinical trials r ecently ( http://www.who. int/vaccine_rese arch