Treatment with cationic liposome-DNA complexes (CLDCs) protects mice from lethal Western equine encephalitis virus (WEEV) challenge.
Having recently characterized a CD-1 outbred mouse model of pathogenesis for Western equine encephalitis virus, we examined the possible protective effects of cationic liposome-DNA complexes (CLDCs) against encephalitic arboviral infection. In this investigation, mice were pre-treated, co-treated, or post-treated with CLDC then challenged with a subcutaneous or aerosol dose of the highly virulent WEEV-McMillan strain, lethal in mice 4-5 days after inoculation. Pre-treatment with CLDCs provided a significant protective effect in mice, which was reflected in significantly increased survival rates. Further, in some instances a therapeutic effect of CLDC administration up to 12h after WEEV challenge was observed. Mice treated with CLDC had significantly increased serum IFN-gamma, TNF-alpha, and IL-12, suggesting a strong Th1-biased antiviral activation of the innate immune system. In virus-infected animals, large increases in production of IFN-gamma, TNF-alpha, MCP-1, IL-12, and IL-10 in the brain were observed by 72h after infection, consistent with neuroinvasion and viral replication in the CNS. These results indicate that strong non-specific activation of innate immunity with an immune therapeutic such as CLDC is capable of eliciting significant protective immunity against a rapidly lethal strain of WEEV and suggest a possible prophylactic option for exposed individuals.
Logue
Christopher H
CH
Division of Vector-Borne Infectious Diseases, Centers for Disease Control, Fort Collins, CO 80521, USA.
Phillips
Aaron T
AT
Mossel
Eric C
EC
Ledermann
Jeremy P
JP
Welte
Thomas
T
Dow
Steve W
SW
Olson
Ken E
KE
Powers
Ann M
AM
D000818:Animals; D001769:Blood / Q000276:immunology; D001921:Brain / Q000276:immunology; D016207:Cytokines / Q000032:analysis / Q000097:blood; D004247:DNA / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage; D004667:Encephalitis Virus, Western Equine / Q000235:genetics / Q000276:immunology*; D004683:Encephalomyelitis, Equine / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D007155:Immunologic Factors / Q000008:administration & dosage*; D007167:Immunotherapy / Q000379:methods*; D008081:Liposomes / Q000008:administration & dosage*; D051379:Mice; D016019:Survival Analysis
D016207:Cytokines; D004337:Drug Carriers; D007155:Immunologic Factors; D008081:Liposomes; D004247:DNA
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