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

Journal Article · · Antiviral Research
 [1];  [2];  [3]
  1. US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD (United States)
  2. US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD (United States); Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
  3. Oncovir, Inc., Washington, DC (United States)
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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. Finally, in the two longest surviving poly-ICLC- treated NHPs, the day 10 serum EBOV titer was reduced 2.1 and 30 fold respectively.

Research Organization:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Organization:
USDOE National Nuclear Security Administration (NNSA); National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH)
Grant/Contract Number:
AC52-07NA27344; 1R01AI067505-01
OSTI ID:
1890794
Report Number(s):
LLNL-JRNL-731581; 882760
Journal Information:
Antiviral Research, Vol. 163; ISSN 0166-3542
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English

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59 BASIC BIOLOGICAL SCIENCES
aqueous/liposomal poly-ICLC
efficacy in mice
TLR+/TLR-3 mice
NHP EBOV titers
NHP liver/kidney enzymes
NHP survival time