Clinical trial of a DIOS Trivalent Haemorrhagic Fever Vaccine (DIOS-HFVac3)

Bringing together cutting edge technologies, we have generated a new vaccine candidate that protects against 3 highly contagious African Haemorrhagic Fever Viruses (HFV), which have significant global epidemic potential. With this technology, we can achieve dramatic improvements to the breadth of protection conferred by vaccines against emerging and re-emerging pathogens. Our DIOS (Digitally designed, Immune Optimised and Selected) technology provides the broadest possible protection against viral variants to limit future outbreaks of highly variable pathogens. In our Innovate Stage 1 project, we achieved clear proof-of-concept for this platform, moving quickly from demonstrating DIOS platform immunogenicity to generate a unique trivalent vaccine candidate. In a second Stage 1 project, animals vaccinated against three diverse viruses - Lassa, Ebola and Marburg were protected from lethal infection. Our top candidate next generation DIOS antigens, targeting these 3 diverse families of HFVs, gave the broadest immune responses and proved stable in the MVA vaccine vector. In the Innovate Stage 2 project we propose to take this to next stage, performing a “first-in-human” clinical trial of DIOS vaccine inserts to demonstrate the safety profile of the DIOS-HFVac3 candidate and its improved breadth of the immune responses in human volunteers.   We have proven that DIOS inserts based on both the DNA vaccine vector pEVAC and the highly immunogenic poxvirus vaccine vector, Modified Vaccinia Ankara (MVA), provide protection from infection. MVA is a safe vector that was used to successfully immunise against smallpox. It is well characterised and has further been modified as a versatile vaccine vector for many pathogens. MVA additionally provides 100% vaccine efficacy against Monkeypox, a disease which is currently causing outbreaks in humans in the same regions where DIOS-HFVac3 would be deployed as a vaccine. It has been demonstrated that cold chain independent vaccine lots of MVA can be produced and we would aim to achieve this with both the pEVAC and MVA DIOS inserts for rapid deployment wherever outbreaks may occur.  Our human clinical trial design will have two arms, one with MVA/DIOS-HFVac3 alone, and the other with co-administration of MVA expressing a fourth HFV found in Africa, namely Crimean-Congo Haemorrhagic fever virus (CCHFV). In collaboration with the MVA-CCHF Innovate clinical trial consortium, GMP lots of MVA-CCHF, made to the same standards as MVA-DIOS-HFVac3, will be used for co-administration. This represents a unique opportunity to evaluate if a tetravalent human VHF vaccine will provide equivalent immunogenicity, and potentially protect humans against 4 VHF pathogens (Lassa, Ebola, Marburg, CCHF) as well as Monkeypox. 
 5. Description of Proposed Idea/Technology