The efficacy of poly-ICLC against Ebola-Zaire virus (EBOV) infection in mice and cynomolgus monkeys

• Published in: Antiviral research Vol. 163; pp. 179 - 184
• Main Authors: Kende, Meir, Paragas, Jason, Salazar, Andres M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2019; Elsevier
• Subjects: Animals; Aqueous/liposomal poly-ICLC; BASIC BIOLOGICAL SCIENCES; Carboxymethylcellulose Sodium - analogs & derivatives; Carboxymethylcellulose Sodium - therapeutic use; Democratic Republic of the Congo; Efficacy in mice; Female; Hemorrhagic Fever, Ebola - drug therapy; Interferon Inducers - therapeutic use; Macaca fascicularis; Mice; Mice, Inbred BALB C; NHP EBOV titers; NHP liver/kidney enzymes; NHP survival time; Poly I-C - therapeutic use; Polylysine - analogs & derivatives; Polylysine - therapeutic use; TLR+/TLR-3 mice; Democratic Republic of the Congo; Aqueous/liposomal poly-ICLC; NHP liver/kidney enzymes; Efficacy in mice; NHP survival time; NHP EBOV titers; TLR+/TLR-3 mice
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2018.12.020

The potential protection of poly-ICLC (Hiltonol®) a double stranded RNA (dsRNA) against EBOV infection was assessed with prophylactic and therapeutic administration to wild type and TLR3-negative mice, and in non-human primates (NHPs) by measuring EBOL serum titers, survival extension, and serum liver and kidney function markers. Various doses of aqueous and liposomal poly-ICLC monotherapy provided robust protection in otherwise lethal murine EBOV challenge models, when treatment is started on the day 0 or one day after virus challenge. There was no advantage of liposomal vs. the aqueous poly-ICLC form. Protection appeared to be independent of TLR-3. NHPs treated with poly-ICLC and challenged with EBOV survived longer but eventually succumbed to Ebola infection. Nevertheless, the liver and kidney serum markers were markedly reduced in the infected and treated NHPs. In the two longest surviving poly-ICLC- treated NHPs, the day 10 serum EBOV titer was reduced 2.1 and 30 fold respectively. •Aqueous and liposomal antiviral poly-ICLC therapy equally protected mice against lethal Ebola virus challenge.•In cynomolgus monkeys aqueous poly-ICLC increased the survival time but all succumbed to the viral infection.•In the longer-surviving monkeys the reduced Ebola virus serum titer, liver and kidney markers were indicative to the efficacy.