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Sterile protection of monkeys against malaria after administration of interleukin-12

Nature Medicine volume 3, pages 80–83 (1997)Cite this article

Abstract

An estimated 300–500 million new infections and 1.5–2.7 million deaths attributed to malaria occur annually in the developing world1, and every year tens of millions of travelers from countries where malaria is not transmitted visit countries with malaria. Because the parasites that cause malaria have developed resistance to many antimalarial drugs, new methods for prevention are required. Intraperitoneal injection into mice of one dose of 150 ng (approximately 7.5 μg per kg body weight) recombinant mouse interleukin-12 (rmlL-12) 2 days before challenge with Plasmodium yoelii sporozoites protects 100% of mice against malaria2. We report that one subcutaneous injection of 10 μg/kg recombinant human IL-12 (rhIL-12) 2 days before challenge with P. cynomolgi sporozoites protected seven of seven rhesus monkeys. Protection was associated with marked increases in plasma levels of interferon-γ (IFN-γ), and relative increases of lymphoid cell messenger RNA coding for IFIM-γ and several other cytokines. We speculate that rIL-12 protects monkeys through IFN-γ-dependent elimination of P. cynomolgi-infected hepatocytes. This first report of rIL-12-induced protection of primates against an infectious agent supports assessment of rhIL-12 for immunoprophylaxis of human malaria.

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Authors and Affiliations

  1. Malaria Program, Naval Medical Research Institute, 12300 Washington Avenue, Rockville, Maryland, 20852, USA

    S.L. Hoffman, J.M. Crutcher, E.D. Franke & M. Sedegah

  2. Division of Microbiology, Central Drug Research Institute, Chatar Mazol Palace, Lucknow, 22601, India

    S.K. Puri, P.P. Singh & G.P. Dutta

  3. Winship Cancer Center, Room 5008,1327 Clifton Road NE, Atlanta, Georgia, 30322, USA

    A.A. Ansari & F. Villinger

  4. Division of of Immunology, Department of Medicine, University of Cincinnati, P.O. Box 670563, 231 Bethesda Avenue, Cincinnati, Ohio, 45267-0563, USA

    F. Finkelman

  5. Hoffmann-La Roche Inc., Building 123, 3rd floor, 340 Kingsland Street, Nutley, New Jersey, 07110, USA

    M.K. Gately

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  1. S.L. Hoffman
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  2. J.M. Crutcher
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  5. F. Villinger
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  6. E.D. Franke
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  8. F. Finkelman
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  9. M.K. Gately
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  10. G.P. Dutta
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  11. M. Sedegah
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Hoffman, S., Crutcher, J., Puri, S. et al. Sterile protection of monkeys against malaria after administration of interleukin-12. Nat Med 3, 80–83 (1997). https://doi.org/10.1038/nm0197-80

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