Classic approaches to vaccine development based on killed or attenuated organisms cannot be used to develop a malaria vaccine due to the difficulty in producing sufficient parasites for large-scale vaccination and the biohazard risks associated with the use of organisms cultivated in human blood. Consequently, current malaria vaccine research has adopted biotechnological approaches to develop a vaccine based on specific malaria parasite antigens. Many different criteria have been applied to select candidate malaria vaccine antigens and several key observations have influenced this selection process. First, it is recognized that a degree of clinical immunity develops after repeated, natural infection with the malaria parasite. Second, it is possible to induce protective immunity against malaria infection under defined experimental circumstances. In the case of immunity to the sexual stages of the parasite, infection of animals and human volunteers with irradiated sporozoites confers a significant degree of immunity to sporozoite infection.