STERILE PROTECTION OF MONKEYS AGAINST MALARIA AFTER ADMINISTRATION OFINTERLEUKIN-12

An estimated 300-500 million new infections and 1.5-2.7 million deaths attributed to malaria occur annually in the developing world(1), 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 dru gs, new methods for prevention are required. Intraperitoneal injection into mice of one dose of 150 ng (approximately 7.5 mu g per kg body w eight) recombinant mouse interleukin-12 (rmIL-12) 2 days before challe nge with Plasmodium yoelii sporozoites protects 100% of mice against m alaria(2). We report that one subcutaneous injection of 10 mu g/kg rec ombinant human IL-12 (rhIL-12) 2 days before challenge with P. cynomol gi sporozoites protected seven of seven rhesus monkeys. Protection was associated with marked increases in plasma levels of interferon-gamma (IFN-gamma), and relative increases of lymphoid cell messenger RNA co ding for IFN-gamma and several other cytokines. We speculate that rIL- 12 protects monkeys through IFN-gamma-dependent elimination of P. cyno molgi-infected hepatocytes. This first report of rIL-12-induced protec tion of primates against: an infectious agent supports assessment of r hIL-12 for immunoprophylaxis of human malaria.