Effects of irradiation on Plasmodium falciparum sporozoite hepatic development: implications for the design of pre-erythrocytic malaria vaccines

Immunization with irradiation-attenuated Plasmodium sporozoites confer protection against live sporozoite challenge. Protection relies primarily on cytotoxic lymphocyte activity against infected hepatocytes, and is suppressed when sporozoites are over-irradiated. Here, we demonstrate that over-irradiated (25-30 krad) Plasmodium falciparum sporozoites invade human hepatocytes and transform into uninucleate liver-trophozoites with the same efficiency as non-irradiated and irradiation-attenuated (12-15 krad) sporozoites. Since hepatocytes infected with over-irradiated non-protective sporozoites are likely to express sporozoite-derived peptide/major histocompatibility complex class I molecules on their surface, our results strongly suggest that sporozoite proteins are not the main immunogens involved in protection, and thus may not per se constitute proper malaria vaccine candidates.