The ‘other vaccine’: Why the Imperial jab offers a different kind of hope in the fight against Covid-19

Robin Shattock won’t say it himself – he is a man of modesty, after all – but more people should be paying attention to his vaccine.

As the race for a Covid-19 jab intensifies, the team at Imperial College London has somewhat flown under the radar. Headlines have instead been dominated by the fast-moving progress of their counterparts at Oxford and elsewhere. In time, though, it feels this could all change.

Because although speed is capital in today’s climate, with speculation mounting over who will be first to deliver a vaccine, the reality is that Prof Shattock and his colleagues have their sights set on a different endgame – one that could revolutionise the field for good.

“This is a completely new technology,” Prof Shattock tells The Independent. “If things go well, we can help to create an important legacy for the UK.”

Simply put, the Imperial vaccine is brilliantly unique. It makes uses of self-amplifying RNA to deliver genetic instructions to human muscle cells, which then go on to produce the ‘spike’ protein found on the surface of Sars-Cov-2.

Spotting what appears to be foreign invaders within the body, the immune system springs into action to produce the necessary antibodies and T-cells. This process will – it’s hoped – leave behind a protective memory that enables the body to tackle the real infection.

The candidates developed by Moderna and Pfizer – both of which are nearing the end of their large-scale efficacy trials – draw from similar technology, but as Prof Shattock points out, they don’t utilise the same amplification process. The Imperial vaccine stands alone in this sense.

“The RNA encodes not just the surface protein of the Sars-Cov-2 virus, it also has enzymes in its backbone that can copy the RNA,” explains Prof Shattock. This means that when injected into humans, it begins replicating the genetic sequence responsible for the Covid spike. “It’s a bit like having a photocopier. After amplification, you’ve got thousands of these plans which are then passed around.”

In theory, this will allows the Imperial team to use a smaller dosage for their vaccine, thereby reducing manufacturing costs. But at this stage, it’s unclear how effective the candidate will be. “That's what wakes you up at night because you don't know if we've been working like crazy to get an amazing result or a disappointing result,” says Prof Shattock.

There are other qualities to the technology platform that Imperial has designed which could carry long-term implications for vaccine manufacturing as a whole.

Aware that he’s beginning to drift into the sort of territory where the finer intricacies of vaccine production become incomprehensible, Prof Shattock plays it safe. “Our vaccine is kind of like the first generation of an iPhone,” he says. There will be “lots of innovations we can build into the vaccine" once it’s proven to work.

“Whatever we see at the end of the year, we know that we can make much better in the future,” he adds. “We're looking to make multiple improvements over the coming years.”

The logistics surrounding the vaccine cold chain is notably expected to complicate the global rollout. Depending on what type of jab is approved, there’s a possibility that doses will need to be transported at temperatures as low as -80C – an expensive and challenging hurdle to overcome, for any country.

But Prof Shattock believes future iterations of his vaccine may be able to circumvent this issue. “We're working on formulations where at least it would be initially stable at refrigerated temperatures, instead of frozen,” he says. “Ultimately, we’re looking at ways to making it stable at room temperature.”

He adds that “we don’t have that for today” but is confident that such a quality will be available in a matter of years – something that could change the game for vaccine manufacturers.

On account of its adaptability, the Imperial candidate feels like it could be future-proof, allowing scientists to tweak and edit the technology platform in response to any pandemics that arise in the decades to come. This, says Prof Shattock, is the vaccine’s “biggest value”.

“In some ways we've been slower than the other groups because it's new and we've had to do more testing,” he adds. “But as the regulators get more familiar with our approach, we think it'll be much faster, because they won't say ‘Well, this has never been in humans.'

“It's going to be so important to have this legacy of an RNA vaccine technology because we certainly see that they've been the fastest. We're the only group in the UK that are pioneering this approach and so it's going to be very crucial to make sure there is this legacy that gives us a competitive edge, and also that response capability for new pandemics.”

As for the immediate threat posed by Covid-19, Prof Shattock envisions that his vaccine will be best served as a regular booster for maintaining immunity, something the Oxford candidate is unlikely to do. Given it uses a live chimpanzee adenovirus to transport elements of Sars-Cov-2 into humans, it’s expected people will develop immunity to the viral vector, preventing the vaccine from being used for future top-ups.

“We need a strategy for reboosting – and our approach is suitable for that,” Prof Shattock says. “You don’t get immunity against the vaccine itself, which is the case with some viral vectors.

“For a scenario where the Oxford vaccine gets rolled out across the UK, that might give people protection for six months to a year, but you then need something to come back and reboost people. That may be where we're best positioned in the UK for providing a benefit.” In this sense, the Imperial vaccine could offer a permanent route out of the pandemic.

For now, though, this is all conjecture. Prof Shattock insists there is still a long way to go for his vaccine, which is approaching the end of its early-stage trial. This will give an indication of whether its safe and effective to use in humans – though large-scale trials will be needed to confirm its efficacy levels, with these expected to take place next January.

On the current trajectory, Prof Shattock believes his candidate could get market authorisation by summer of next year, before being rolled out in the second half of 2021 – just in time for a potential winter boost for the UK’s most vulnerable.

One potential spanner in the works is funding. Whereas the Oxford vaccine has the backing of AstraZeneca, meaning millions of doses can be manufactured at-risk ahead of the anticipated rollout, the Imperial team doesn’t yet have a pharmaceutical giant standing by their side.

“We are dependent on others,” the professor says. The majority of financial backing has come from the UK government and other philanthropic sources. And if the data released from the phase 1 trial isn’t encouraging, there’s a chance the money could be cut. “Decisions will be based on what the data looks like: ‘Is it good enough to go forward?’ But they'll also be looking at the state of play across the vaccine field: ‘Is it needed for the UK and other markets?’”

Why, then, hasn’t Imperial entered into an agreement with big pharma? “We had tentative discussions with partners, but at that stage nobody was jumping up and down and saying they wanted us,” says Prof Shattock. In using brand-new, previously untested technology – unlike their rivals – the Imperial vaccine posed too much of a risk. But with all the signs pointing in the right direction, there’s good reason to believe this will change in the near future.

Still, ever the realist, Prof Shattock isn’t getting too ahead of himself. The past eight months have been long and brutal, and the Imperial team – comprised of roughly 20 scientists – knows full well that the race is only half run.

“We're having to be very careful that people aren’t suffering from burnout because they are stretched to do more than they've ever done before,” says the professor. “In the first six months everything is really exciting – you've got that kind of first wind. But now it's becoming a marathon not a sprint, so we need to make sure everyone is pacing themselves.”