Towards a thermostable dual yellow fever/Lassa fever virus vaccine and therapeutic strategies against the Lassa and related mammarenaviruses.

The Lassa fever virus (LASV) causes a deadly viral hemorrhagic disease in West-Africa (~300.000 cases and ~5.000 deaths/year). Lassa fever (LF) is mostly transmitted through exposure to a rodent (genus Mastomys). Also person-to-person transmission occurs, which is in particular problematic for health care workers. An estimated 59 million people are at risk and large outbreaks occurred in the past; LASV has a high potential for widespread epidemics. There is no vaccine for the prevention; ribavirin is used for the treatment, but its effectivity is questionable. Yellow fever (YF) is another hemorrhagic fever virus endemic in the same region as LASV. A highly efficient YF-vaccine is available which requires however a strict cold-chain. Consequently, many are not vaccinated and die because of YF. Our first aim is to develop, using our proprietary PLLAV-vaccine platform technology, a highly thermostable dual YF/LF vaccine. To that end, T- and B-cell epitopes of the LASV (and other mammarenaviruses) will be expressed on highly immunogenic viral like particles (based on the HBVcore). These will be launched from a PLLAV-plasmid that encodes the yellow fever live-attenuated vaccine virus that carries these transgenic sequences. Efficacy will be studied in mouse (infection) models. Our second aim is to make a start, using a chemogenomics approach, mapping the druggable genome of LASV/mammarenaviruses, this in an effort to boost the search for potent and safe antiviral drugs