The flu, caused by seasonal influenza epidemics and occasional pandemics, remains a serious health threat associated with substantial morbidity, mortality and economic loss due to sickness leave. Direct-acting antivirals (DAAs) that inhibit virus replication, and prophylactic vaccines are currently the most effective antiviral strategies. However, the emergence of numerous DAA- and vaccine-resistant virus strains presses the need to develop improved drugs against different influenza variants and subtypes.
AcTaferons (Activity by Targeting interferons) are a novel class of engineered interferons that maximally take advantage of a sophisticated, natural defense system that evolutionary arose to combat viral infections. Cells infected with a virus naturally produce the alarm signal type I interferon (IFN), which upon binding to the IFN receptor on infected and neighbouring cells activates an antiviral response that interferes with the viral replication and spread throughout the body. IFN binding on immune cells further stimulates our immune system to fight the infection. Based on their antiviral and immunostimulatory effects, type I interferons were believed to be the miracle drug to tackle viruses. However, clinical IFN applications remained limited as IFN drugs cause severe side effects due to unwanted IFN binding to IFN receptors present all over the body, resulting in widespread, aspecific action of the drug. AcTaferon circumvents these side effects by selective targeting of IFN to specific cell types. AcTaferon remains inactive “en route” through the body and unveils its antiviral activity only on specific target cells. This project aims to generate virus-targeted AcTaferons (O1) and to evaluate the prophylactic and therapeutic potential of virus- and immune cell-targeted AcTaferons to restrict influenza infection in vitro (O2 and O3) and in vivo (O4).
