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

Authors

  • O. Silvie,

    1. INSERM U511 Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, CHU Pitié-Salpêtrière, Université Pierre et Marie Curie, Paris, France,
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  • J. P. Semblat,

    1. INSERM U511 Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, CHU Pitié-Salpêtrière, Université Pierre et Marie Curie, Paris, France,
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    • *

      These authors contributed equally to the work.

  • J. F. Franetich,

    1. INSERM U511 Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, CHU Pitié-Salpêtrière, Université Pierre et Marie Curie, Paris, France,
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    • *

      These authors contributed equally to the work.

  • L. Hannoun,

    1. Service de Chirurgie Digestive Hépato-biliaire et Transplantation Hépatique, Hôpital Pitié-Salpêtrière, Paris, France and
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  • W. Eling,

    1. Department of Medical Microbiology, University of Nijmegen, Nijmegen, the Netherlands
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  • D. Mazier

    Corresponding author
    1. INSERM U511 Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, CHU Pitié-Salpêtrière, Université Pierre et Marie Curie, Paris, France,
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: Professor D. Mazier, INSERM U511 Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, CHU Pitié-Salpêtrière, Université Pierre et Marie Curie, 75013 Paris, France (e-mail: mazier@ext.jussieu.fr).

Summary

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.

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