Liposome-mediated immunotherapy against respiratory influenza virus infection using double-stranded RNA poly ICLC

The use of liposome delivery technology to enhance the antiviral activity o f poly ICLC tan immunomodulating dsRNA) while decreasing its intrinsic toxi city is evaluated in this study. The antiviral efficacies of free and lipos ome-encapsulated poly ICLC were evaluated and compared using a lethal respi ratory influenza A virus infection in mice. The toxicity profiles of free a nd liposome-encapsulated poly ICLC were compared by determining the extent of hypothermia and loss in body weights in mice pretreated with these drugs . Poly ICLC was encapsulated in cationic liposomes prepared by the freeze dry ing method, To determine the antiviral efficacies of free and liposome-enca psulated poly ICLC, mice were intranasally pretreated with two doses of pol y ICLC (free or liposomal, 1 mg/kg/dose) given 48 h apart. Al various times post pretreatment mice were intranasally challenged with 10 LD50 mouse-ada pted influenza A/PR/8 (H1N1) virus. The survival rates of the mice were det ermined at day 14 post infected and compared to the untreated control mice. Results indicate mice pretreated with liposome-encapsulated poly ICLC with in 3 weeks prior to virus challenge were completely protected (100% surviva l compared to 0% for the untreated control group, p < 0.001), while window of protection provided by free unencapsulated poly ICLC was 12 days. When t he toxicity profiles of free and liposome-encapsulated poly ICLC were compa red, it was found that hypothermia and body weight loss induced by poly ICL C were either completely mitigated or significantly reduced in mice given e quivalent doses of poly ICLC in the liposome-encapsulated form, These results suggest that liposomes are an excellent drug carrier for poly ICLC, that liposome-encapsulated poly ICLC may provide a safe and effectiv e immunotherapeutic approach for the prevention of respiratory influenza vi rus infections. Published by Elsevier Science Ltd.