Prof Robin Shattock would have liked slightly longer to develop the revolutionary approach to vaccines that he is pretty sure will not only save lives in the Covid-19 pandemic but become the norm for vaccine development within five years.
His team at Imperial College were working on Ebola and Lassa fever vaccines using new technology but had not got as far as human trials when a novel coronavirus started to kill thousands of people in Wuhan, China.
Animal data told them they were on the right track, but it is now Covid-19 that will prove or disprove whether the approach, using what they call self-amplifying RNA, is a breakthrough.
He is careful not to over-promise, but it is clear he backs his own horse over 120 other contenders in the effort to develop a coronavirus vaccine. “Of course, or I wouldn’t be doing it,” Shattock told the Guardian.
“I’m cautiously optimistic that it will work as well as anything else that is being developed because it induces good immune responses in animal models, and we predict it will be the same in humans and it will be very safe because we are using such low doses.
“What we don’t know is what level of immunity is required to prevent infection. If we only need a tiny bit, the majority of vaccines out there will probably work. That will be fantastic for the world.
“If we need a certain level of immune response that is high then we may see some vaccines are more successful than others. I would hope ours will be one of the successful ones, but there is no guarantee until we get the data that shows it works.”
The Imperial vaccine is based on bits of genetic code, rather than bits of the virus itself. The code is inserted in fat droplets into the muscle of the arm, which then makes the spike protein for which the Sars-CoV-2 virus is famous. This induces the immune system to go into action, producing antibodies to fight it and hopefully creating a memory of the virus as an enemy invader to be repelled in case of genuine infection.
Shattock is aiming for a vaccine that will treat all the billions of people on the planet, however small their country’s GDP. That’s the real beauty of this approach, he believes: it’s very safe, uses very little material and can be scaled up very quickly.
And it’s going to be cheap, around £2 to £3 a dose, he thinks, which is chips for a brand-new vaccine. The first vaccines for human papillomavirus (HPV), which can cause types of cancer, cost around £300 per course.
Imperial has philanthropic funding from Morningside Ventures, founded by the Chan family of Hong Kong, and has formed a social enterprise called VacEquity Global Health to bring the vaccine to the world. Royalties will be waived for low-income countries. Shattock says they may charge higher prices for wealthy countries in order to give the vaccine to the poorest at no cost.
If it’s a race, Imperial will not win it. “We are not going to be first unless others fail,” he said. If that matters, it is because all the demand and funding will focus on the first vaccine that works, though there will be issues around affordability and scaling up.
The vaccines being developed in the US are likely to stay there, with the Trump administration securing every dose that can be produced to protect Americans first. “I suspect if they work, they will be so busy meeting US demand that there are always going to be parts of the world that can’t access them,” Shattock said. “The idea that a single vaccine will be rolled out in a timely fashion around the world I think is very naive.”
The UK government has put significant funding into Oxford University and Imperial’s attempts. The US has also invested in Oxford, but Shattock is not sorry it hasn’t offered anything to him. “In some ways it makes life easier. They have so much money that it also comes with a kind of pull. I think we would get very distracted if we were in that huge race in the US,” he said.
It’s unlikely the first vaccines will be 100% effective, and the protection they give may wear off after a time. Shattock said it was quite possible that the Oxford University/Astra Zeneca prototype, which is ahead of the field as the first in large human trials, and the Imperial vaccine could be used together.
“That’s not a surprise. If you use two different approaches – one to prime the immune system, and change to another to boost it, it often gives you a better response. One of the uncertainties about the AstraZeneca vaccine is whether it could be used for reboosting the immune system if you need an annual or five-yearly booster,” he said.
Oxford is using a traditional approach, delivering the vaccine through a mild cold virus called an adenovirus. That should teach the immune system to fight the coronavirus, but it’s possible the antibodies may next time reject the cold virus as well, so extra booster doses won’t work so well. The Imperial vaccine, on the other hand, which is two shots to begin with, one month apart, can be given as often as needed.
So is Shattock’s vaccine better? “I think that’s a difficult judgment call to make,” he said. “If what we see in animals translates to humans, we will have a different quality of immune response. That’s probably because we can give two doses. I think we will see higher levels of antibodies. Whether that makes a difference in protection or not, again, is an unknown.”
Imperial will start its efficacy trials in humans in October. “We should know whether the vaccine works by the end of the year,” he said. “We have put in place the ability to make 85m doses for the UK.” At two doses each, that could cover 42.5 million adults. “We can make more, but we know we can guarantee we can make that many doses. We can cover the UK without any problem at all.”
He thinks the more vaccines there are that work, the better, because that will give more coverage around the world. Imperial’s can be produced in very large quantities so quickly because it uses very little material, but Shattock said: “We need to partner with manufacturers around the world to do that.” That could be a huge pharma company such as AstraZeneca, but more likely, he thinks, it will be a variety of smaller companies that currently work on small margins based in different parts of the world, producing it in South America, India, Australia and so on to get global spread.
The success rate of vaccines at this stage of development is 10%, Shattock says, and there are already probably 10 vaccines in clinical trials, “so that means we will definitely have one”.
Other vaccines getting big support in the US are Johnson and Johnson’s, which uses an adenovirus like Oxford’s, and Moderna’s, which uses an RNA approach like Imperial’s but with a dose that is 100 times bigger. “I suspect their vaccine and ours will look quite similar in terms of immune response, but we are just using much less material. And they won’t be interested in developing world markets because they are a billion-dollar enterprise and need to make big returns on their investment.” BioNTech in Germany is testing several RNA candidates, one of which looks similar to Imperial’s.
While Shattock hopes the Imperial vaccine works against Covid-19, his team see it very much as the future. “The next time there is a pandemic, we hope this technology will be ready to be produced in many parts of the world much, much more rapidly. We are at a transition point. In five years’ time probably everybody will be using this sort of technology for outbreak pathogens.”
It’s fast and it’s cheap. If it works, it may mean vaccines not only against viral outbreaks but also against the endemic neglected diseases that afflict low-income countries, where there has been little incentive in the past for companies to get involved.