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 lipid DNA complexes (CLDC) 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 CLDC 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 12 hours after WEEV challenge was observed. Mice treated with CLDC had significantly increased serum IFN-γ, TNF-α, 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-γ, TNF-α, MCP-1, IL-12, and IL-10 in the brain were observed by 72 hours 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.

Liposomes as vaccine delivery systems: a review of the recent advances

“…CLDC-vaccinated mice were challenged with virulent WEEV. CLDC pretreatment provided increased survival and higher cytokine levels, strong T H 1 activation and protective immunity against lethal WEEF [Logue et al 2010]. An influenza A virus vaccine adjuvanted with CLDC or alum was tested by Hong and colleagues.…”

Liposome-Antigen-Nucleic Acid Complexes Protect Mice from Lethal Challenge with Western and Eastern Equine Encephalitis Viruses

“…Although ODN and PIC can each induce an antiviral immune response within the host, the responses differ in expression profile, cellular localization, and signaling pathways (23). Importantly, WEEV, EEEV, and VEEV are exquisitely sensitive to experimental immunomodulation with ODN or PIC (12)(13)(14).…”

“…The nucleic acid components of CLNCs, unmethylated CpG oligodeoxynucleotides (ODN) or the doublestranded RNA (dsRNA) analog polyinosinic-poly(C) (PIC), are agonists of Toll-like receptor 9 (TLR9) and Toll-like receptor 3 (TLR3), respectively (12)(13)(14). Treatment with ODN or PIC results in strong cytokine/chemokine induction, establishing an antiviral state within the host.…”

Encephalitic Development in Alphaviral Infection

“…Protection is associated with increased serum and brain levels of IFN-gamma, TNF-alpha, and IL-12 as well as increases in MCP-1 and IL-10 in the brain after neuroinvasion. Thus, a strong-non specific activation of the innate immune system with a distinct Th1 bias elicits protection in the absence of pre-exisiting memory response (Logue, et al, 2010). Administration of an E1 adenovirus vectored antibody also induced a strong WEE specific T-cell response associated with increased secretion of IFN- (Swayze, et al, 2010).…”