Prophylaxis with cationic liposome-DNA complexes protects hamsters from phleboviral disease

Importance of liposomal delivery and CpG motifs

Brian B. Gowen, Jeff Fairman, Steven Dow, Ryan Troyer, Min Hui Wong, Kie Hoon Jung, Peter Melby, John D. Morrey

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Cationic liposome-DNA complexes (CLDC) are cationic/neutral lipid carriers complexed with plasmid DNA that when administered systemically results in a robust TH1 cytokine response. CLDC have been shown to be effective in prophylaxis and therapeutic treatment of animal models of viral disease. To determine the contribution of liposomal delivery and CpG content of the plasmid DNA to the efficacy of CLDC; plasmid, CpG-free plasmid DNA, or CpG-containing oligodeoxynucleotides (ODN) with and without liposomes, as well as poly(I:C12U), were evaluated for their ability to elicit protection against lethal Punta Toro virus (PTV, Bunyaviridae, phlebovirus) challenge in hamsters. CLDC-containing plasmid significantly improved survival, decreased systemic and liver viral loads, and reduced liver damage due to progression of viral infection. Mouse-reactive ODNs complexed with liposomes failed to protect hamsters, whereas ODNs known to cross-react with human and mouse (CpG 2006) or non-liposomal poly(I:C12U) showed survival benefit but did not limit liver injury. Liposomes complexed with a non-CpG motif-containing plasmid reduced liver viral load and tissue damage, but did not protect hamsters from death. To evaluate the mechanisms of the enhanced activity of CLDC, microarray experiments examined differences in the gene expression profile. The results suggest a broad TH1 response elicited by liposomal delivery of a diverse sequence containing CpG and non-CpG elements may be a more effective antiviral treatment than other nucleic acid based immunotherapeutics.

Original languageEnglish (US)
Pages (from-to)37-46
Number of pages10
JournalAntiviral Research
Volume81
Issue number1
DOIs
StatePublished - Jan 2009
Externally publishedYes

Fingerprint

Liposomes
Cricetinae
Plasmids
DNA
Poly I
Liver
Virus Diseases
Viral Load
Phlebovirus
Bunyaviridae
Survival
Oligodeoxyribonucleotides
Oligonucleotide Array Sequence Analysis
Transcriptome
Nucleic Acids
Antiviral Agents
Therapeutics
Animal Models
Cytokines
Viruses

Keywords

  • Antiviral
  • CpG
  • Liposomes
  • Phlebovirus
  • Punta Toro virus
  • Rift Valley fever

ASJC Scopus subject areas

  • Virology
  • Pharmacology

Cite this

Prophylaxis with cationic liposome-DNA complexes protects hamsters from phleboviral disease : Importance of liposomal delivery and CpG motifs. / Gowen, Brian B.; Fairman, Jeff; Dow, Steven; Troyer, Ryan; Wong, Min Hui; Jung, Kie Hoon; Melby, Peter; Morrey, John D.

In: Antiviral Research, Vol. 81, No. 1, 01.2009, p. 37-46.

Research output: Contribution to journalArticle

Gowen, Brian B. ; Fairman, Jeff ; Dow, Steven ; Troyer, Ryan ; Wong, Min Hui ; Jung, Kie Hoon ; Melby, Peter ; Morrey, John D. / Prophylaxis with cationic liposome-DNA complexes protects hamsters from phleboviral disease : Importance of liposomal delivery and CpG motifs. In: Antiviral Research. 2009 ; Vol. 81, No. 1. pp. 37-46.
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