Use of attenuated sporozoites in the immunization of human volunteers against falciparum malaria

Abstract

Three human volunteers were successfully protected against sporozoite challenge by immunization with attenuated sporozoites of the Tamenie strain of Plasmodium falciparum from Ethiopia. The immunizing sporozoites were attenuated by exposing infected Anopheles stephensi mosquitos to X-rays at a dose of at least 120 Gy (12 000 rad). These irradiated, infected mosquitos were allowed to feed upon volunteers, thereby inoculating sporozoites into their blood stream. During the 10- to 38-week period of immunization, volunteers were exposed 6-8 times, at irregular intervals, to a total of 440-987 irradiated infected mosquitos. Protection against challenge by nonirradiated infected mosquitos lasted for at least 8 weeks, but not 16 weeks, after the last immunization with irradiated sporozoites. By contrast, volunteers who were exposed to a total of 200 or fewer irradiated infected mosquitos on 2-4 occasions were not protected upon challenge. Immunization by a sufficient number of irradiated mosquitos infected with the chloroquine-sensitive Tamenie strain from Ethiopia also protected against challenge with the chloroquine-resistant Marks strain of P. falciparum from Viet Nam. The results obtained in these studies suggest that immunization with attenuated sporozoites may be a useful method of protecting small groups of nonimmune individuals living in endemic areas. These findings should encourage further efforts to develop a sporozoite vaccine against human malaria.