MIchelle Deaton (University of Denver)
Scott Pegan (University of Denver)
Stuart Nichol (CDC)
- In vitro data available
This invention relates to a genetically modified hemorrhagic fever virus that can be used as an effective live vaccine agent. Hemorrhagic fever evades the human immune response using the viral ovarian tumor domain (vOTU) protease, which inhibits critical host-immunity functions. The present genetically modified virus has a vOTU protease with decreased ability to remove ubiquitin (Ub) and ISG15 tags from proteins in cells it infects. Thus, the virulence is reduced, creating an immunogenic and non-pathogenic virus for use as a live vaccine against Crimean-Congo hemorrhagic fever (CCHF) virus. Unlike strains with complete ablation of the vOTU protease, the present modified virus retains enough activity for replication in a human cell line, making vaccine production possible. This technology may be used to create vaccines or therapeutics for other nairoviruses, including the Dugbe, Hazara, and Nairobi sheep disease viruses.
- Development of vaccines or therapeutics for CCHF virus and other nairoviruses, including Dugbe, Hazara and Nairobi sheep disease viruses.
- Increased safety for CCHF laboratory research (Biosafety Level 2).
- Use of human cell lines allows large-scale manufacturing of vaccines.
- vOTU domain-disruption may be used to develop vaccines for all nairovirus viruses affecting humans and/or livestock.