One Health and accelerating Vaccines for Ebola and Lassa (OVEL)

The One Health and accelerating Vaccines for Ebola and Lassa (OVEL) is a focused comparative One Health vaccine project based on the need to understand future threats of zoonotic virus spill-overs from their natural animal reservoirs to humans. This information is important to develop the most effective protective vaccines to prevent future human outbreaks. A disproportionally high number of emerging and re-emerging diseases are caused by RNA viruses and many are carried naturally by animals (Heeney, J Internal Med, 2006). Their genomes are notoriously variable due to the high mutation rate that occurs during replication. These accumulate over time and results in evolvolution of the viruses as they circulate in their natural animal reservoir populations. Thus, these variant viruses carried by animals are a risk to human health and may spill-over to people who share the same environment. If some viral variants arise and are able to adapt to use human cell receptors and if they are able to escape immune defences, they may become highly infectious and cause large disease outbreaks. Vaccines are only as good as the immune targets (the viral protein (antigen) presented by vaccines) of the pathogen that they are designed for. If the antigen changes, vaccines fail to protect. In most cases current vaccine candidates against RNA viruses are from past human outbreaks with little or no information of future risks from viral variants carried in animal reservoirs, especially those with the potential for animal to human (zoonotic) transmission. We propose to establish an extended viral sequence database derived from animal reservoirs for two virus families which cause viral haemorrhagic diseases in geographically overlapping regions of West Africa. By gaining new molecular/genomic and antibody data from animal hosts, we will acquire an understanding of the infection dynamics and viral persistence in their natural reservoirs, while providing essential viral diversity data in reservoirs to discover new vaccine antigens and accelerate truly protective vaccine design. We will acquire Lassa/Arenavirus sequence diversity data from a comprehensive survey of the natural rodent hosts (Mastomys natalensis and other rodent reservoir species) in Nigeria where documented Lassa outbreaks occur in states with cases caused by diverse isoaltes of Lassa fever virus. A second reservoir viral sequence database is likely to arise from a complementary study funded by the UK GCRF award to Prof J Wood based from sampled bat colonies in Ghana which Ebolavirus antibody and antigen positive animals have been found. Equipped with this information on the sequence diversity of viruses in animal reservoirs which threaten to spill-over to humans, we will be able to design better vaccine antigens for more effective and broadly protective vaccines. We will achieve this using a new accelerated vaccine development platform using cutting edge technologies to achieve dramatic improvements in vaccine efficacy and the speed of vaccine development. We will use the new EVAC (Emerging viral Vaccine Antigen Construct) platform vaccine technology we previously developed with Innovate-UK funding. The EVAC platform, which significantly accelerates vaccine development, merges (i) sequences of outbreak pathogens and their reservoirs in West Africa, (ii) broadly anti-viral neutralising monoclonal antibodies derived from viral haemorrhagic fever survivors, (iii) computational modelling methodologies, (iv) synthetic gene technology, and (v) in vivo immune selection and vaccine efficacy readouts. The end products are novel vaccine antigens to trigger the broadest spectrum of protective immune responses using Digitally Designed, Immune Optimised and Selected (DIOS) vaccine antigens against re-emerging RNA viruses Lassa Fever and Ebola viruses.