saRNA SARS-CoV-2 vaccine

We will rapidly progress a synthetic vaccine against the novel Coronavirus into human
studies within months. We have determined the genetic sequence (code) for the dominant
surface exposed protein of the virus, the key target for protective immune responses. We
have modified this sequence to express a highly stabilised version of the protein,
maximising its potential to evoke protective antibodies. We have used this modified
sequence to generate a ribonucleic acid (RNA) based vaccine that can be amplified within
cells following injection, maximising its expression. Our RNA vaccine delivers the genetic
instructions that tell muscles to make the viral surface protein which alerts the immune
system to make protective antibodies. The advantage of our fully synthetic manufacturing
process means that millions of doses can be made within weeks. This project will support
clinical grade manufacturing of our candidate vaccine, preclinical safety testing and
healthy volunteer studies to assess safety and immune potency of our vaccine. Should
this first phase be successful we would progress to wider clinical testing, including studies
to determine its protective effects against natural infection before making our vaccine
widely available.

This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project.

This project aims to rapidly progress a self-amplifying RNA (saRNA) vaccine against the
2019 novel Coronavirus (SARS-CoV-2) to first in human studies (phase I) within a matter
of months. Within 14 days of accessing the sequence we have already designed and
constructed a candidate saRNA vaccine expressing a pre-fusion stabilised conformation
of the native surface glycoprotein (S-protein). This design maximises the potential for
induction of neutralising antibodies while minimising the induction for off-target responses
to post-fusion conformations. We have engaged key manufacturing partners able to
generate GMP material not only for phase I/II studies according to a very tight schedule
but also with the capability to rapidly scale to millions of doses should this be required.
This cutting-edge nucleic acid vaccine platform has been specifically designed for rapid
manufacture and deployment in the event of an outbreak. SaRNA offers significant
advantages over other nucleic acid vaccine platforms yielding exponentially higher levels
of protein expression than messenger RNA (mRNA) or DNA. The self-amplifying
properties of saRNA mean that much lower doses are required to induce protective
immunity, providing a significant advantage to manufacturing costs and speed.
Additionally, saRNA is not limited by anti-vector immunity and is safe to administer to
individuals unable to receive live attenuated vaccines (e.g. children and the
immunocompromised). The Target Product Profile (TPP) is a vaccine that can be rapidly
manufactured at low cost and elicit protective immunity across all at risk populations within
6 weeks of administration, with the potential for repeat boosting as required.