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

A multivalent haemorrhagic fever vaccine based on synthetic replicating ribonucleic acid 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 ). Our program aims to develop a multivalent vaccine against the most common human viral haemorrhagic fevers ( Ebola, Marburg and Lassa fever virus). The choice of targets is based on strong scientific evidence that gene-based approaches can protect against infection in preclinical models. 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 haemorrhagic viruses can easily be combined. This may be critical to the global response against emerging haemorrhagic 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 haemorrhagic viruses but is also more likely to show cross-protection against novel variants that may arise in the future. In Part 1 of this project (now complete) we successfully completed the heavy lifting required to move our RNA platform from a research process through to fully established robust and validated manufacturing process, confirming the potency of the produced product in preclinical models. In this Part 2 project we will manufacture clinical grade material (GMP), conduct the required preclinical toxicology and early evaluation of the vaccine in a phase I human clinical trial designed to assess the safety and immunogenicity of our pan-haemorrhagic fever vaccine. Our ability to deliver on the aggressive timelines required to move from manufacture through to completion of a first in human clinical trial within two-year grant funding period is only possible due to the robustness and speed of our manufacturing process and the unique competency of the assembled team in translating vaccine concepts from the bench to the bedside . Ultimately our vision is to use our vaccine platform to ensure UK preparedness for any eventual pandemic and to make vaccines globally available in the event of any outbreak situation. Our approach will ensure appropriate costing for low and middle-income countries and be readily available to organizations focused on global health (e.g. MSF and WHO): 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 stable multivalent vaccine that can elicit protective immunity against the most common human viral haemorrhagic fevers following one or two immunisation across all populations, has potential for boosting in the absence of anti-vector immunity, and can be rapidly manufactured at low cost.