EML-VAC: Multivalent replicon vaccine against Ebola, Marburg and Lassa viruses

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A multivalent hemorrhagic fever vaccine based on synthetic replicating ribonucleic acid (RepRNA) would provide one of the fastest and most cost-effective approaches to stop viral outbreaks at their source. This affords significant advantages over more conventional vaccine approaches such as viral vectors, and attenuated pathogens and would be safer in individuals unable to receive live attenuated vaccines (e.g. children and the immunocompromised). This vaccine may also find utility as a booster that can be used in combination with existing vaccines (e.g. rVSV-EBOV). The fully synthetic manufacture and ease of production provides the potential to produce hundreds of thousands of doses within a matter of weeks where the individual vaccine components targeting different hemorrhagic viruses can easily be combined. This may be critical to the global response against emerging hemorrhagic viral infections, as the nature of the next outbreak cannot be reliably predicted. In this respect the proposed multivalent vaccine has potential not only to protect against multiple known hemorrhagic viruses but is also more likely to show cross-protection against novel variants that may arise. The proposed vaccine can be effectively freeze-dried providing a portable and stable product that can withstand temperature oscillations without the requirement for a cold chain. The program aims to develop a multivalent vaccine against the most common human viral hemorrhagic fevers (two Ebola viruses, Marburg virus and Lassa virus). The choice of targets is based on strong scientific evidence that gene based approaches can protect against infection in preclinical models. This Part 1 project will support vaccine characterisation, proof of concept ‘in vivo’ studies and process finalisation, such that on completion of the project everything will be in place to rapidly move into early phase I human trials upon successful Part 2 funding. Our vision is to ensure appropriate costing for low and middle income countries and to make the vaccine readily available to organizations focused on global health (e.g. MSF and WHO), as these groups have historically been the first to detect, and/or respond to an outbreak, and are therefore ideally positioned to assist in implementing any vaccination strategy. Our Target Product Profile (TPP) is a temperature stable multivalent vaccine that can elicit protective immunity against the most common human viral hemorrhagic fevers following a single immunisation across all populations (adults, children and the immunocompromised), has potential for boosting in the absence of anti-vector immunity, and can be rapidly manufactured at low cost.