Professor Robin Shattock is leading efforts to develop an RNA vaccine for COVID-19.
An innovative approach to COVID-19 vaccine development using RNA offers advantages in speed and scalability, if tests prove successful.
Although effective vaccines may be identified in 12 to 18 months, it could take significantly longer before they become globally available.
The world must learn from the COVID-19 pandemic and ensure sufficient investment is made to safeguard against future pandemics.
Work to fast-track the development of a coronavirus vaccine received a boost last week as the UK government announced £42.5 million in funding for the country’s two leading efforts at Oxford University and Imperial College London. Last Thursday, Oxford University’s programme, led by Professor Sarah Gilbert, became Europe’s first to enter human trials while the Imperial College team aim to begin clinical trials in June. This takes the total number of coronavirus vaccine clinical trials started in 2020 to 11.
Heading up the Imperial team is Professor Robin Shattock. In 2019, he spoke at the World Economic Forum’s Annual Meeting in Davos about the new techniques he was developing to facilitate the rapid development, testing and – crucially – local production of vaccines. Together, these techniques help to ensure that outbreak responses can be made quickly, with no region or country left behind. We spoke to him to learn how his team’s efforts were progressing and to get his thoughts on the global response so far.
In 2019, you warned audiences in Davos of the threat posed by a pandemic, calling for action to ensure the world could respond quickly if one should occur. How did it feel to watch COVID-19 spread and how do you think the global effort to find a vaccine is doing so far?
It’s been an interesting time to live through. When we presented in Davos, we were saying that these things will happen, but we were not thinking it was going to happen so soon, or that it would be a coronavirus. Everybody was predicting it would probably be an avian influenza outbreak.
In terms of the global response, it’s good news that there are many different vaccines being developed, with I think over 90 at the last count. There is a degree of coordination but all these groups are working independently on their own approaches or technology. That’s not necessarily a bad thing – given there’s so much risk in developing a vaccine, that means the risk is spread out, and I think it’s pretty clear that some groups will come through with an effective vaccine.
Your team has been working on developing a vaccine for COVID-19 since early February. Could you describe for our readers how a typical vaccine is made and how your approach using RNA differs?
The traditional vaccine approaches usually rely on physically growing the virus. This can be done either by growing the virus in huge volumes, 10s or 100s of thousands of litres, and then inactivating it, or by culturing viruses over time to gradually weaken them until they are safe. Both methods take a long time before they are ready for clinical use and require a lot of virus for an effective dose.
Our approach is to focus on just the genetic code of the spike protein on the surface of the virus and use that as our vaccine. When the vaccine is injected into the body, muscle cells naturally “amplify” it by producing copies of the spike protein which the immune system detects as a threat. This trains the body’s immune system to defend against SARS-CoV-2 through being able to recognise the spike protein if it encounters it again.
What are the advantages to working with RNA?
Using RNA allows us to be fast because the genetic sequence can be made synthetically in the lab, and because it can self-amplify, we need only a very low dose of the vaccine for it to be effective – we can make the equivalent of a million doses in one litre of reaction material. This allows us to scale up very quickly and it is feasible to be making 10s of millions of doses per week from our lab. Adding more vaccine platforms working in parallel will only increase production capacity further.
Is distributed production ready to help and what other measures can be taken to ensure vaccines reach all those in need?
Right now, the distributed production mechanism is not there. Manufacturing facilities around the world are not set up with the same technology, so identical methods cannot be used. There is also a need for harmonization of regulatory approval to ensure that when a vaccine is cleared for use in one location, other manufacturing sites around the world can move swiftly to scale production.
I do not expect that such a network will get up and running in time to contribute significantly to the COVID-19 response. When effective vaccines are identified they will probably still be produced through a more traditional approach of working with very large manufacturers. However, developing such distributed production capabilities should be a key part of strengthening global resilience after this crisis has passed.
An example of what more can be done is that of the Serum Institute in India and some others that are offering to make vaccines royalty-free to ensure they are available to as many as possible without the obstacle of high cost.
A graphic showing two vaccine production approaches separated by a vertical red line. On the left a single large manufacturing plant with a large crowd of people and on the right many small manufacturing plants with small groups of people.
A distributed approach to vaccine production would help distribute it faster and more widely.
Image: R. Shattock, Imperial College London
Some researchers are reporting lower than expected levels of viral antibodies in people who have recovered from COVID-19, possibly implying that any immunity gained will be temporary. Will a vaccine be able to stimulate a stronger response, giving longer lasting immunity?
Yes, a vaccine must do better than natural immunity and there is strong evidence that it will. COVID-19 is a respiratory infection and those with a mild infection will not be exposed to much virus because it will only be on their respiratory surfaces. The natural immune response to such an infection will be much lower than that generated from a potent vaccine injection. If the vaccine does not generate a strong response, then it should not be rolled out to the general population.
For a vaccine to be highly effective, it should prevent infection in over 80% of vaccinated people and give them immunity for a minimum of a year (which would allow for annual boosting) but ideally longer.
In normal times, vaccine development takes many years but today we are seeing accelerated timelines coupled with pressure from governments, the media and the public. As a researcher, how are you dealing with this?
It’s difficult to get the right balance. It’s important for people to understand that we’re moving faster than anybody’s moved before because we’re aiming to have a fully tested vaccine within 12-18 months when normally it would be five to eight years, or longer. That said, when the need is as urgent as it is today, even 12–18 months seems slow.
There is a need to temper expectations slightly though, as while we will have vaccines tested soon, we won’t have vaccines globally available for a much longer time period.
Vaccine hesitancy has reduced the efficacy of public vaccination programs in some areas, leading to outbreaks of measles and other preventable diseases. Are you at all concerned that such behaviour could limit the potential of a coronavirus vaccine?
Right now, I think people want a vaccine. I don’t think there will be much hesitancy about having a vaccine while COVID-19 is at the forefront of our minds. The issue with vaccines is they’re so successful in preventing the disease that it goes away and the reason they’re necessary becomes less apparent.
What is the World Economic Forum doing about the coronavirus outbreak?
If in two, three or more years’ time, we’ve had a successful vaccine and we’re not seeing new COVID-19 infections, people may increasingly choose not to be vaccinated. That could be due to hesitancy or simply it not being top of their priority list since the virus no longer appears to be a threat. This could lead to outbreaks popping up and effective public engagement strategies will be needed to minimize the risk of this occurring.
What message would you like to leave our readers with?
We are already seeing the massive impact of this pandemic on the economies of the world. We must learn from this and make the necessary investments to limit the impact of future pandemics now. The investment needed is tiny compared with the economic and human toll of another pandemic. It just makes total financial sense and anything else doesn’t. The world needs an insurance policy against pandemics
