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

Antiviral Res. 2019 Mar:163:179-184. doi: 10.1016/j.antiviral.2018.12.020. Epub 2019 Jan 3.

Abstract

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.

Keywords: Aqueous/liposomal poly-ICLC; Efficacy in mice; NHP EBOV titers; NHP liver/kidney enzymes; NHP survival time; TLR+/TLR-3 mice.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carboxymethylcellulose Sodium / analogs & derivatives*
  • Carboxymethylcellulose Sodium / therapeutic use
  • Democratic Republic of the Congo
  • Female
  • Hemorrhagic Fever, Ebola / drug therapy*
  • Interferon Inducers / therapeutic use*
  • Macaca fascicularis
  • Mice
  • Mice, Inbred BALB C
  • Poly I-C / therapeutic use*
  • Polylysine / analogs & derivatives*
  • Polylysine / therapeutic use

Substances

  • Interferon Inducers
  • Polylysine
  • poly ICLC
  • Carboxymethylcellulose Sodium
  • Poly I-C