saRNA SARS-CoV-2 vaccine

Lead Research Organisation: Imperial College London

Abstract

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.

Technical Summary

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.

Publications

10 25 50
 
Description Invited to give lecture 'Ensuring quality processes in Phase III vaccine trials' for Industry (CEPI initiative, audience SAARC countries); 11th Dec. 2020.
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact The audience was healthcare practitioners in Asia who are engaged in research activities. My talk focused on the challenge of conducting clinical trials in a pandemic and I shared my experience of implementing a COVID-19 vaccine trial.
 
Description Keynote lecture: Beyond Coronavirus: Vaccination and the COVID-19 Pandemic, Queen's Belfast; 21st Jan 2021.
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact 351 people registered and 181 joined on the day from across Queen's University Belfast and the general public. There were 50 questions submitted on a range of topics. Of note, these included questions about the UK decision to have a longer gap in order to increase the coverage of COVID-19 vaccines, and vaccine hesitancy.
URL https://www.youtube.com/watch?v=GiK4URYqgKI&feature=youtu.be
 
Description Ad Hoc application to NIHR for additional funds to evaualte three higher doses of the saRNA vaccine in the saRNA SARS-CoV-2 vaccine trial
Amount £902,207 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 08/2020 
End 03/2022
 
Description Donation to the saRNA SARS Cov 2 vaccine trial
Amount £440,000 (GBP)
Organisation J P Moulton Charitable Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2020 
End 08/2021
 
Description MRC/UKRI & NIHR. Funding also provided through Imperial Philanthropic funds, COVID-19 Response Fund (funding not included in £2.6m value below)
Amount £2,626,916 (GBP)
Funding ID MC_PC_19076 (MRC/UKRI) and NIHR 
Organisation Imperial College London 
Sector Academic/University
Country United Kingdom
Start 03/2020 
End 03/2022
 
Title COVAC 1 trial database 
Description Database for data collection to the COVAC 1 clinical trial to assess the safety of a coronavirus vaccine in healthy men and women: 'A first-in-human clinical trial to assess the safety and immunogenicity of a self-amplifying ribonucleic acid (saRNA) vaccine encoding the S glycoprotein of SARS-CoV-2, the causative agent of COVID-19'. Data collection for 7 clinical sites in Open Clinica v4. https://doi.org/10.1186/ISRCTN17072692 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? No  
Impact 414 participants recruited, numerous staff from 7 centres trained in data entry and have access to the database. Trial reports 2021. First electronic data capture database for the unit, well received. 
 
Description COVAC 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution COVAC1 clinical trial management provided by MRC CTU at UCL for 'A first-in-human clinical trial to assess the safety and immunogenicity of a self-amplifying ribonucleic acid (saRNA) vaccine encoding the S glycoprotein of SARS-CoV-2, the causative agent of COVID 19' Eudract No. 2020-001646-20 IRAS ID: 279315 Protocol writing and revisions. TSC & IDMC established and actively meeting. Statistical analysis and trial management expertise at CTU who set up and hold the database. Database training for sites - done remotely. Protocol writing and revisions. For COVAC 1, there are 7 recruiting centres; 414 participants recruited in total; 409 completed 2 vaccinations. Imperial College Healthcare NHS Trust: Imperial Clinical Research Facility & St. Mary's Hospital University Hospital Southampton NHS Foundation Trust Chelsea and Westminster Hospital NHS Foundation Trust St. George's University Hospitals NHS Foundation Trust University of Surrey University College London Hospitals NHS Foundation Trust Established links with overseas research teams: South African, Chile, Peru and Brazil for further collaborations where the scientific direction warrants.
Collaborator Contribution Chief Investigator: Dr. Katrina Pollock (Imperial Clinical Research Facility) reviewed the trial documentation, oversight of safety reporting and responsible for recruiting the majority of participants. Scientific Lead for COVAC Programme: Prof. Robin Shattock designed the vaccine and oversight of central immunology laboratory. Imperial College created a COVID-19 Response Fund as a means for donors to contribute to a pooled fund that will give the College the flexibility to quickly support high-impact projects in the university's efforts to tackle COVID-19: https://www.imperial.ac.uk/giving/covid-19-funds/response-fund/
Impact Multi-disciplinary collaboration: clinical, immunology, statistical, manufacturing.
Start Year 2020
 
Title COVAC 1 clinical trial 
Description COVAC 1 clinical trial to assess the safety of a coronavirus vaccine in healthy men and women: 'A first-in-human clinical trial to assess the safety and immunogenicity of a self-amplifying ribonucleic acid (saRNA) vaccine encoding the S glycoprotein of SARS-CoV-2, the causative agent of COVID-19'. Funded by NIHR and Imperial Philanthropic funds. https://doi.org/10.1186/ISRCTN17072692 
Type Therapeutic Intervention - Vaccines
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2021
Development Status Under active development/distribution
Impact This first in human experience of a self-amplifying RNA vaccine is near completion. 
URL https://www.isrctn.com/ISRCTN17072692
 
Company Name VAXEQUITY LTD. 
Description VaxEquity was founded in 2020 by Imperial College and Morningside. VaxEquity develops transformative RNA therapeutics and vaccines using its next generation self-amplifying RNA platform.VaxEquity uses saRNA to provide extended duration of protein expression. This enables lower doses to be used for vaccines and higher protein levels to be achieved for therapeutics. VaxEquity is pioneering a next generation approach by modifying its self-amplifying RNA (saRNA) to modulate the innate immune response and thereby overcoming current limitations. The flexibility of the Company's platform ensures that its broad pipeline of assets can be designed, developed and manufactured rapidly and at scale. 
Year Established 2020 
Impact AstraZeneca has provideed VaxEquity with £195 million of R&D funding and has invested in the biotech as part of a long-term effort to optimize and validate the saRNA platform. In return, AstraZeneca will gain a chance to work with VaxEquity on up to 26 drug targets.
 
Description Appearance on Newsround CBBC 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Prof Robin Shattock appeared on Newsround to do an Q and A about making a vaccine to prevent COVID-19.

In the programme Dr Chris answers a question from Teddy who asks: "How does this nasty virus stop?"

Dr Chris goes to Imperial College, London, where a team of scientists are working really hard to come up with a vaccine.

He speaks to Professor Robin Shattock, who is breaking all of the normal vaccine-making rules in trying to make a cure for coronavirus.

https://www.bbc.co.uk/newsround/52534775
Year(s) Of Engagement Activity 2020
URL https://www.bbc.co.uk/newsround/52534775
 
Description Appearance on Question Time 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Professor Robin Shattock appeared on BBCs Question Time on the 3rd February 2022 as a panel member. This was a special episode in which unvaccinated people were encourage to attend the show to discuss vaccine hesitancy. Professor Shattock tried to debunk the myths that COVID-19 vaccines are dangerous by explaining that there is a large amount of safety data collected from the current COVID vaccines as they have been given to billions of people around the world and that serious side effects are extremely rare.
Year(s) Of Engagement Activity 2022
 
Description Article in the Guardian on the volunteers participating in the Imperial Vaccine trial 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Thousands of ordinary people around Britain volunteered to take part in the Imperial College London coronavirus vaccine trial. Who are they, what motivated them to take part, and what's it been like?

These portraits were taken for Team Halo, an initiative that goes behind the scenes with the scientists trying to develop a Covid vaccine

https://www.theguardian.com/society/gallery/2020/nov/13/it-came-in-a-locked-box-uk-covid-vaccine-volunteers-in-pictures
Year(s) Of Engagement Activity 2020
URL https://www.theguardian.com/society/gallery/2020/nov/13/it-came-in-a-locked-box-uk-covid-vaccine-vol...
 
Description COVAC1 Participant Webinar 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Study participants or study members
Results and Impact We held a participant webinar in order to share the results of the dose-ranging part of the COVAC1 trial. COVAC1 evaluated a new type of vaccine candidate against SARS-CoV2 - it was a self-amplifying RNA vaccine.

We evaluated 6 different doses for safety and immunogenicity.

We held the webinar to explain the results before they were in the public domain on the Lancet pre-print server. The participants were very engaged, had lots of questions - some of which were difficult to answer. Participants were very interested to see their immune responses and we agreed to provide these, having emphasised that they were not to be used to make clinical decisions.
Year(s) Of Engagement Activity 2021
URL https://www.imperial.ac.uk/news/222553/self-amplifying-rna-covid-19-vaccine-technology-safe/
 
Description Operation Ouch TV programme 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Operation Ouch, the series for children shown on the CBBC has featured Imperial researchers that were working on the Imperial vaccine
The programme transmitted on (24th February 2021) on CBBC. Episode 2 (which is the first episode of this series, after the virus special in the summer) is on iPlayer via this link: https://www.bbc.co.uk/iplayer/episode/m000r6nv/operation-ouch-series-9-episode-2
Year(s) Of Engagement Activity 2021
URL https://www.bbc.co.uk/iplayer/episode/m000r6nv/operation-ouch-series-9-episode-2