Treatment of Yellow Fever Virus with an Adenovirus-Vectored Interferon, DEF201, in a Hamster Model

Abstract

Interferon (IFN) is an innate immune response protein that is involved in the antiviral response during viral infection. Treatment of acute viral infections with exogenous interferon may be effective but is generally not feasible for clinical use due to many factors, including cost, stability, and availability. To overcome these limitations, an adenovirus type 5-vectored consensus alpha IFN, termed DEF201, was constructed as a potential way to deliver sustained therapeutic levels of systemic IFN. To demonstrate the efficacy of DEF201 against acute flaviviral disease, various concentrations of the construct were administered as a single intranasal dose prior to virus infection, which resulted in a dose-responsive, protective effect in a hamster model of yellow fever virus (YFV) disease. A DEF201 dose of 5 ؋ 10 7 PFU/animal administered intranasally just prior to YFV challenge protected 100% of the animals, while a 10-fold lower DEF201 dose exhibited lower, although significant, levels of protection. Virus titers in the liver and serum and levels of serum alanine aminotransferase were all significantly reduced as a result of DEF201 administration at all doses tested. No toxicity, as indicated by weight loss or gross morbidity, was observed in non-YFV-infected animals treated with DEF201. Protection of YFV-infected animals was observed when DEF201 was delivered as early as 7 days prior to virus challenge and as late as 2 days after virus challenge, demonstrating effective prophylaxis and therapy in a hamster model of disease. Overall, it appears that DEF201 is effective in the treatment of YFV in a hamster model.

Protection against Chikungunya virus induced arthralgia following prophylactic treatment with adenovirus vectored interferon (mDEF201)

“…A replication-deficient adenovirus type 5 vector containing a gene for mouse IFN-α, mDEF201, is administered intranasally where it enters nasal epithelial cells and expresses the transgene (Julander et al, 2011). This results in the production of systemic levels of IFN several hours after treatment (Wu et al, 2007).…”

BCX4430, a Novel Nucleoside Analog, Effectively Treats Yellow Fever in a Hamster Model

“…Mortality is not dependent on virus challenge dose (8), and mortality rates between 50% and 100% have been observed after challenge with the same virus challenge dose. This hamster model has been used to evaluate candidate YF antiviral agents (11)(12)(13)(14)(15) and vaccines (16,17) and was used in the current study.…”

Infergen Stimulated Macrophages Restrict Mycobacterium tuberculosis Growth by Autophagy and Release of Nitric Oxide

“…Undeniably, previous references have indicated the efficiency of the IFNs therapy in treating yellow fever, chronic hepatitis B (HBV), hepatitis C (HCV) and ebola virus infections4142. They augment the synthesis of several key antiviral mediators, including 2′-5′ oligoadenylate synthetase (2′-5′ A synthetase) and protein kinase R4344.…”