title: Treatment with cationic liposome-DNA complexes (CLDCs) protects mice from lethal Western equine encephalitis virus (WEEV) challenge.
abstract: 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.
authors.affiliation: Division of Vector-Borne Infectious Diseases, Centers for Disease Control, Fort Collins, CO 80521, USA.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Logue
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Phillips
authors.forename: Eric C
authors.initials: EC
authors.lastname: Mossel
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Ledermann
authors.forename: Thomas
authors.initials: T
authors.lastname: Welte
authors.forename: Steve W
authors.initials: SW
authors.lastname: Dow
authors.forename: Ken E
authors.initials: KE
authors.lastname: Olson
authors.forename: Ann M
authors.initials: AM
authors.lastname: Powers
mesh_terms: 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
chemical_list: D016207:Cytokines; D004337:Drug Carriers; D007155:Immunologic Factors; D008081:Liposomes; D004247:DNA
references.citation: J Virol. 2009 Apr;83(8):3429-35
references.pmid: 19176616
references.citation: Cancer Immunol Immunother. 2001 Dec;50(10):503-14
references.pmid: 11776372
references.citation: Nature. 2000 Dec 7;408(6813):740-5
references.pmid: 11130078
references.citation: Nature. 2007 Jul 26;448(7152):501-5
references.pmid: 17618271
references.citation: J Immunol. 2001 Sep 15;167(6):3324-8
references.pmid: 11544321
references.citation: J Med Entomol. 2001 May;38(3):393-9
references.pmid: 11372964
references.citation: Virology. 2007 Nov 25;368(2):273-85
references.pmid: 17681583
references.citation: J Immunol. 2006 Jun 15;176(12):7335-45
references.pmid: 16751377
references.citation: Virology. 2007 Apr 10;360(2):454-60
references.pmid: 17118420
references.citation: J Virol. 2001 Nov;75(21):10431-45
references.pmid: 11581411
references.citation: Oncogene. 2008 Jan 7;27(2):181-9
references.pmid: 18176599
references.citation: Antiviral Res. 2008 Jul;79(1):71-9
references.pmid: 18358544
references.citation: J Immunol. 2010 Feb 1;184(3):1445-54
references.pmid: 20042590
references.citation: Hum Vaccin. 2009 Mar;5(3):141-50
references.pmid: 18690014
references.citation: Nat Rev Immunol. 2003 Feb;3(2):133-46
references.pmid: 12563297
references.citation: J Exp Med. 1989 Dec 1;170(6):2081-95
references.pmid: 2531194
references.citation: Eur J Immunol. 1995 Apr;25(4):1129-32
references.pmid: 7737285
references.citation: Biotechniques. 2002 Oct;Suppl:16-20, 22, 24-9
references.pmid: 12395924
references.citation: Immunity. 2006 Jan;24(1):93-103
references.pmid: 16413926
references.citation: J Exp Med. 1994 Jul 1;180(1):223-31
references.pmid: 7516409
references.citation: Annu Rev Immunol. 2002;20:709-60
references.pmid: 11861616
references.citation: Trends Immunol. 2006 Nov;27(11):525-32
references.pmid: 16979939
references.citation: J Exp Med. 1993 Feb 1;177(2):523-7
references.pmid: 8426121
references.citation: J Leukoc Biol. 2005 Jan;77(1):71-9
references.pmid: 15496451
references.citation: J Virol. 2005 May;79(9):5374-85
references.pmid: 15827152
references.citation: Antiviral Res. 2003 Jan;57(1-2):101-11
references.pmid: 12615306
references.citation: Cancer Res. 2000 Jun 1;60(11):2955-63
references.pmid: 10850443
references.citation: J Gen Virol. 2009 Aug;90(Pt 8):1848-1858
references.pmid: 19403754
references.citation: Nat Immunol. 2002 May;3(5):423-4
references.pmid: 11976718
references.citation: J Immunol. 1999 Aug 1;163(3):1552-61
references.pmid: 10415059
references.citation: J Infect Dis. 2005 Oct 1;192(7):1173-82
references.pmid: 16136459
references.citation: J Leukoc Biol. 2004 Feb;75(2):163-89
references.pmid: 14525967
references.citation: Antiviral Res. 2006 Mar;69(3):165-72
references.pmid: 16430975
references.citation: Gene Ther. 1999 Nov;6(11):1867-75
references.pmid: 10602382
references.citation: J Immunol. 1995 Aug 1;155(3):1420-7
references.pmid: 7636207
references.citation: J Immunol. 2001 Oct 1;167(7):3555-8
references.pmid: 11564765
references.citation: J Gen Virol. 2009 Jun;90(Pt 6):1382-1391
references.pmid: 19264662
references.citation: Science. 1993 Jul 9;261(5118):209-11
references.pmid: 7687073
references.citation: Adv Drug Deliv Rev. 2008 Apr 29;60(7):847-57
references.pmid: 18280611
references.citation: Nat Rev Immunol. 2004 Jul;4(7):499-511
references.pmid: 15229469
references.citation: Clin Vaccine Immunol. 2009 May;16(5):699-705
references.pmid: 19279167
references.citation: J Virol. 2009 Dec;83(23):12432-42
references.pmid: 19793821
references.citation: Antiviral Res. 2009 Jan;81(1):37-46
references.pmid: 18840471
references.citation: BMC Neurol. 2006 May 19;6:18
references.pmid: 16709257
references.citation: J Virol. 2009 Oct;83(20):10571-81
references.pmid: 19656875
references.citation: Nature. 2005 Apr 7;434(7034):772-7
references.pmid: 15800576
references.citation: Infect Immun. 2009 Apr;77(4):1579-88
references.pmid: 19179415
references.citation: Nat Immunol. 2000 Jul;1(1):83-7
references.pmid: 10881180
references.citation: Am J Trop Med Hyg. 1988 Mar;38(2):447-52
references.pmid: 2833129
references.citation: Springer Semin Immunopathol. 2005 Jan;26(3):221-9
references.pmid: 15592841
references.citation: Virology. 2009 Dec 5;395(1):121-32
references.pmid: 19782381