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

SummaryImmunization 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.