Pre- and post-exposure protection against Western equine encephalitis virus after single inoculation with adenovirus vector expressing interferon alpha

Abstract

Western equine encephalitis virus (WEEV) is a positive-sense, single-stranded RNA virus which is transmitted to equines and humans through mosquito bites. WEEV infects the central nervous system with severe complications and even death. There are no human vaccine and antiviral drugs. We investigated whether adenovirus-mediated expression of interferon alpha could be used for pre- and post-exposure protection against a lethal WEEV challenge in mice. A human adenoviral vector (Ad5-mIFNalpha) expressing mouse interferon alpha was constructed. We found that Ad5-mIFNalpha provided 100% protection against various WEEV strains in mice after a single intramuscular inoculation at 24 h, 48 h or 1 week before the challenge. When given as a single inoculation at 6 h after the challenge, Ad5-mIFNalpha delayed the progress of WEEV infection and provided about 60% protection. Our findings suggest that adenovirus-mediated expression of interferon alpha can be an alternative approach for the prevention and treatment of WEEV infection.

Alpha interferon as an adenovirus-vectored vaccine adjuvant and antiviral in Venezuelan equine encephalitis virus infection

“…The construction and properties of replicationdefective adenovirus type 5 containing no VEEV sequence (RAd) or expressing serogroup IA/B structural proteins (RAd/VEEV # 3) have been described previously . Replicationdefective adenovirus type 5 expressing murine IFN-a subtype 5 (Ad5-mIFNa) has been described previously (Wu et al, 2007). VEEV strain Trinidad donkey (TrD), from serogroup IA/B, was supplied by Dr R. E. Shope (University of Texas Medical Branch, Galveston, TX, USA).…”

“…Delivery by an adenovirus vector offers an alternative strategy for improving the half-life and the therapeutic effect of IFN-a. A single injection of an adenovirus vector expressing IFN-a is effective against foot-and-mouth disease virus (FMDV; Chinsangaram et al, 2003) and another alphavirus, Western equine encephalitis virus (WEEV) (Wu et al, 2007). The ability of IFN-a to protect against VEEV disease was therefore tested in this study, using an adenovirus vector for delivery.…”

“…This method was adapted from that described by Wu et al (2007). Briefly, 5610 5 L929 cells were plated into each well of a six-well plate.…”

Evaluation of Different Strategies for Post-Exposure Treatment of Ebola Virus Infection in Rodents

“…Preparations with a ratio of at least 1:200 infectious to total particle were used in this study. AdHu5 expressing recombinant IFN-α (DEF201) were provided by Defyrus Incorporated, ON and manufactured as described [44].…”

Encephalitic Development in Alphaviral Infection

“…These animals lacked observable IFN in serum. The authors hypothesize that the discrepancy between serum IFN and protection could be due to continued higher levels of IFN in the brain providing protection following decrease of serum IFN (Wu, et al, 2007b). Thus, when given prior to infection, IFN-treatment provides rapid, lasting protection, and is indicative of the importance of a rapid, strong innate immune response.…”