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

Kumaki, Yohichi; Salazar, Andres M.; Wandersee, Miles K.; Barnard, Dale L.

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.