Emerging Viral Vaccine Antigen Insert Consortium (EVAC)

Of the emerging and re-emerging diseases a disproportionate number (37%) are caused by RNA viruses (Heeney, J Internal Med, 2006), notoriously variable due to their intrinsically high mutation rate. Vaccines are only as good as the immune targets (antigens or gene inserts) of the pathogen that they encode. In most cases current vaccine candidates against RNA viruses are limited by the viral strain used as the vaccine insert, which is often chosen based on availability of a wild-type strain rather than by informed design. By bringing together cutting edge technologies we can achieve dramatic improvements in vaccine efficacy against new viral variants based on outbreak sequence data to generate synthetic optimised vaccine inserts to give the broadest possible vaccine protection against future outbreaks of variable RNA viruses. We will generate new vaccine candidate inserts for a wide variety of emerging and re-emerging viral agents including Ebola, Marburg, Lassa, Zika, MERS, Chikungunya, Dengue and others. Our new platform vaccine technology merges (1) sequences of outbreak pathogens, (2) broadly anti-viral neutralising monoclonal antibodies (BNmAb) derived from outbreak survivors, (3) computational modelling methodologies, (4) synthetic gene technology and antigen display technology, (5) high throughput viral binding and neutralisation screens, and (6) in vivo immune selection and vaccine efficacy readouts. The end products are novel immunogens to trigger the broadest spectrum of protective immune responses using Digitally Designed, Immune Optimised and Selected (DIOS) vaccine inserts against emerging/re-emerging RNA viruses. Towards this goal we propose two streams: Stream I) Proof of concept (this application). Within 12 months, we will demonstrate proof of concept by targeting the broader family of Ebola viruses by delivering next generation vaccine inserts designed to be slotted into existing clinically trialled vaccine vectors to compare improvements in immune responses, the breadth of protection, durability and efficacy. We will deliver new DIOS vaccine inserts into existing candidate Ebola vaccine vectors to enable direct comparison in head to head clinical trials. Stream II) During stream 1 we will have established proof of concept and prepared our technology pipeline to address other outbreak RNA viral disease vaccines needs such as Lassa Fever virus and Zika virus. The collaborating team has the technology operational (under previous Gates Foundation/HIV funding) and we have a proven track record of working together and delivering (Ewer et al, NEJM, 2016). This new platform will improve the UK’s vaccine arsenal to emerging viral diseases, and ensure that the UK is at the forefront of the global fight against future disease outbreaks.