HFVac4: A Quadrivalent Viral Haemorrhagic Fever Vaccine for Africa

We have developed a pre-clinical trivalent Haemorrhagic Fever Vaccine (HFV) candidate able to combat three important African haemorrhagic fever viruses: Lassa Fever virus (LASV), Ebola (EBOV) and Marburg (MARV) viruses. Separately, a fourth vaccine monovalent candidate against Crimean-Congo Haemorrhagic Fever (CCHF) has been developed by our collaborator Miles Carroll is about to start Phase 1 trials. These highly pathogenic RNA viruses cause regular epidemics, and outbreaks cause significant morbidity and mortality with significant impact on human health in low- and middle-income countries (Heeney, J Internal Med, 2006). Lassa fever is endemic to Western Africa with estimates ranging between 300,000 to a million infections, with 5,000 deaths per year. Its overlapping geographic distribution with other Viral Haemorrhagic Fevers (VHFs) caused by Filoviruses such as Ebola virus (EBOV) complicated the early clinical diagnosis of Ebola virus disease in the 2014/2015 West African outbreak.

A combined VHF vaccine eliciting protection against the four major haemorrhagic fevers in West and Central Africa would be of great benefit. Currently there are no licensed vaccines for these infections. A single vaccine to protect against all these regionally important VHFs that is economic, easy to produce, readily deployable and temperature stable in the absence of continuous cold chain storage is highly desirable. The Modified Vaccinia Ankara (MVA) vaccine platform is a non-replicating, third generation smallpox vaccine vector and one of the safest, most advanced large antigen payload recombinant pox-based vaccine vectors in human clinical trials (Cottingham & Carroll, Vaccine, 2013). MVA is a robust vector system capable of co-expressing multiple transgenes facilitating potent promoters and stable insertion sites (Orubu et al, PLOSone, 2012). By designing an MVA vector strategy to combining antigens from these 3 pathogens together with CCHF in MVA we aim to cover all 4 major overlapping causes of VHFs in Africa with the inherent protection against Monkeypox afforded by the MVA vaccine vector.

To develop a pan-Viral Haemorrhagic Fever vaccine covering the 4 major causes of VHF, this VHFvac4 project brings the synergistic new platform technologies together from the CCHF-MVA project (Carroll, Innovate UK with the HFVac3 projects). Using the DIOS synthetic immune optimised vaccine inserts which provide the broadest possible vaccine protection, our trivalent vaccine demonstrated robust proof of concept (PoC) in the Tri-LEMvac consortium. We now take the next bold step to expand this to the 4th major VHF, CCHF as an all in one multivalent pan VHF vaccine for Africa.