nation with irradiated sporozoites can protect humans against malaria, suggesting that immunization with appropriate sporozoite and liver-stage antigens can prevent infection in individuals bitten by malaria-infected mosquitoes. In addition, repeated natural infections with the malaria parasite induce immune responses that can prevent disease and death in infected individuals, and the administration of serum antibodies obtained from repeatedly infected adults can control malaria infections in children who have not yet acquired protective immunity. These data suggest that immunization with appropriate blood-stage antigens can drastically reduce the consequences of malaria infection. Finally, experimental evidence shows that immunization with sexual-stage antigens can generate an immune response that prevents parasite development in the vector, offering a strategy for interrupting malaria transmission.

Prospects for the development of malaria vaccines are enhanced by the availability of suitable methods for evaluating candidate antigens. These include protocols that allow human volunteers to be safely infected with malaria, and the identification of many areas in the world where more than 75 percent of individuals can be expected to become infected with malaria during a three-month period. In contrast to vaccines for diseases of low incidence, for which tens of thousands of immunized and nonimmunized controls must be studied over several years, malaria vaccines could be evaluated in selected areas in fewer than 200 volunteers in less than a year.

Developments in molecular and cellular biology, peptide chemistry, and immunology provide the technological base for engineering subunit vaccines composed of different parts of the malaria parasite, an approach that was not possible 10 years ago. During the last 5 years, more than 15 experimental malaria vaccines have undergone preliminary testing in human volunteers. Although none of these vaccines has proven suitable for clinical implementation, progress has been made in defining the parameters of a successful vaccine and the stage has been set for further advancement.

Despite the inherent attractiveness and promise of this approach, there remain a number of obstacles to vaccine development. With the exception of the erythrocytic (blood) stages of P. falciparum, human malaria parasites cannot be readily cultured in vitro, limiting the ability of researchers to study other stages of this parasite and all stages of the other three human malaria parasite species.

In vitro assays, potentially useful for screening candidate vaccines for effectiveness, do not consistently predict the level of protective immunity seen in vivo. The only laboratory animals that can be infected with human malaria parasites are certain species of nonhuman primates, which are not naturally susceptible to these organisms. This makes it difficult to com-



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