Prophylaxis with cationic liposome‐DNA complexes protects hamsters from phleboviral disease: importance of CpG motifs?

Abstract

Cationic liposome‐DNA complexes formed with plasmid DNA (CLDC), CpG‐free plasmid DNA, or CpG‐containing oligodeoxynucleotides (ODN) were evaluated for their ability to elicit protective immunity against Punta Toro virus (PTV) challenge in the hamster infection model. Liposome‐DNA formulations were administered by the intraperitoneal route 4 h prior to inoculation of a highly lethal PTV inoculum. Survival outcomes, as well as reduction of viral burden and liver disease, were assessed. A dose of CLDC containing 30 μg of plasmid significantly improved survival outcome, decreased systemic and liver viral loads, and reduced liver pathology compared to animals receiving placebo. Known mouse‐ and human‐reactive ODNs delivered in liposome complexes failed to protect challenged hamsters. Treatment with liposomes containing non‐CpG motif‐containing plasmid reduced liver virus titers compared with untreated or CpG treated, but did not protect hamsters from death. This suggests that while elements other than CpG motifs may stimulate a response sufficient to control viral replication in the target organ, the empty vector plasmid DNA backbone with CpG islands appears to be critical to stimulating protection against mortality in the PTV hamster model. Supported by contract grant NO1‐AI‐15435 from the Virology Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health.