Prophylactic and therapeutic intranasal administration with an immunomodulator, Hiltonol ® (Poly IC:LC), in a lethal SARS-CoV-infected BALB/c mouse model.

Autor: Kumaki Y; Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Science, 5600 Old Main Hill, Logan, Utah State University, Logan, UT 84322, USA. Electronic address: yohichi.kumaki@usu.edu., Salazar AM; Oncovir, Inc., Washington, DC, USA., Wandersee MK; Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Science, 5600 Old Main Hill, Logan, Utah State University, Logan, UT 84322, USA., Barnard DL; Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Science, 5600 Old Main Hill, Logan, Utah State University, Logan, UT 84322, USA.
Jazyk: angličtina
Zdroj: Antiviral research [Antiviral Res] 2017 Mar; Vol. 139, pp. 1-12. Date of Electronic Publication: 2016 Dec 09.
DOI: 10.1016/j.antiviral.2016.12.007
Abstrakt: Hiltonol ® , (Poly IC:LC), a potent immunomodulator, is a synthetic, double-stranded polyriboinosinic-polyribocytidylic acid (poly IC) stabilized with Poly-L-lysine and carboxymethyl cellulose (LC). Hiltonol ® was tested for efficacy in a lethal SARS-CoV-infected BALB/c mouse model. Hiltonol ® at 5, 1, 0.5 or 0.25 mg/kg/day by intranasal (i.n.) route resulted in significant survival benefit when administered at selected times 24 h prior to challenge with a lethal dose of mouse-adapted severe acute respiratory syndrome coronavirus (SARS-CoV). The infected BALB/c mice receiving the Hiltonol ® treatments were also significantly effective in protecting mice against weight loss due to infection (p < 0.001). Groups of 20 mice were dosed with Hiltonol ® at 2.5 or 0.75 mg/kg by intranasal instillation 7, 14, and 21 days before virus exposure and a second dose was given 24 h later, prophylactic Hiltonol ® treatments (2.5 mg/kg/day) were completely protective in preventing death, and in causing significant reduction in lung hemorrhage scores, lung weights and lung virus titers. Hiltonol ® was also effective as a therapeutic when give up to 8 h post virus exposure; 100% of the-infected mice were protected against death when Hiltonol ® was administered at 5 mg/kg/day 8 h after infection. Our data suggest that Hiltonol ® treatment of SARS-CoV infection in mice leads to substantial prophylactic and therapeutic effects and could be used for treatment of other virus disease such as those caused by MERS-CoV a related coronavirus. These properties might be therapeutically advantageous if Hiltonol ® is considered for possible clinical use.
(Published by Elsevier B.V.)
Databáze: MEDLINE
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