Protective immunity against acute phleboviral infection elicited through immunostimulatory cationic liposome-DNA complexes.
Cationic liposome-DNA complexes (CLDC) have been demonstrated to induce potent antitumor activities. The ability of these complexes to elicit protective immunity against viral infections has not been fully explored. Here we report findings on the use of CLDC as an antiviral agent in a mouse model of acute phleboviral (Punta Toro virus) disease. CLDC treatment of mice challenged with Punta Toro virus (PTV) resulted in dramatic increases in survival and reduced viral burden and other parameters indicative of protection against disease. CLDC were effective when administered by intraperitoneal and intravenous routes and elicited protective immunity when given within 1 day of virus challenge. Treatments administered 36 h or longer after challenge, however, were not effective in preventing mortality or disease. CLDC treatment induced release of a number of potential antiviral cytokines including IFN-gamma, IL-12, and IFN-alpha. Taken together, our findings indicate that non-specific immunotherapy with CLDC appears to be an effective treatment for blocking PTV-induced disease and suggests that further exploration in other viral disease models may be warranted.
Gowen
Brian B
BB
Institute for Antiviral Research, Utah State University, Logan, UT 84322, United States. bgowen@cc.usu.edu
Fairman
Jeff
J
Smee
Donald F
DF
Wong
Min-Hui
MH
Jung
Kie-Hoon
KH
Pace
Anne M
AM
Heiner
Matthew L
ML
Bailey
Kevin W
KW
Dow
Steven W
SW
Sidwell
Robert W
RW
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D002044:Bunyaviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy* / Q000821:virology; D016207:Cytokines / Q000097:blood; D004279:DNA, Viral / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008081:Liposomes / Q000008:administration & dosage / Q000276:immunology*; D008099:Liver / Q000821:virology; D051379:Mice; D016856:Phlebovirus / Q000276:immunology*; D016019:Survival Analysis; D019562:Viral Load
D000276:Adjuvants, Immunologic; D016207:Cytokines; D004279:DNA, Viral; D008081:Liposomes