Why we don't believe any variant will be able to defeat jab completely

Why we don’t believe any Covid variant will be able to defeat our jab completely: Creators of the Oxford vaccine SARAH GILBERT and CATH GREEN give a very reassuring answer to the question that haunts us all

It’s the awe-inspiring story of the decade – the efforts of two women to create the Oxford vaccine that has been at the forefront of our fight against Covid. Last week Sarah Gilbert and Cath Green told how they and their teams worked round the clock to make the jab in just months, rather than years. Here, in the second extract from their new book, the pair reveal how they are now focused on tackling Covid variants that threaten our freedom – and the fake news being spread about the vaccine…

Sarah Gilbert

Wednesday, January 27, 2021.

I felt a mix of giddy elation and frustration. I hadn’t quite known what to do with myself all morning. After much not-very-patient waiting, I was finally going to be vaccinated.

There had, of course, been no happy ending yet. Along with Cath and her team, I was working very hard on planning the route to making new versions of the vaccine based on the new variants.

The clinical trials team, run by our colleague Andy Pollard, was still following participants to see if any developed Covid symptoms, and analysing blood samples to see how long their immunity lasted.

Another team, led by Tess Lambe, was still in the lab every day.

There had been no let-up, no chance to take stock or celebrate, and the long days in the lab that had felt like a fun sprint in the optimistic days of early summer had become a marathon-like slog.

With case numbers still very high, we all felt at risk, for ourselves but also for the work we needed to do.

I felt a mix of giddy elation and frustration. I hadn’t quite known what to do with myself all morning. After much not-very-patient waiting, I was finally going to be vaccinated, writes Sarah Gilbert, pictured above

We explored many avenues to try to get the team vaccinated, and finally I received an email inviting me to book an appointment.

Joining the socially distanced queue outside the clinic, I felt elated. I had received a vaccine of my own design before, but as part of a safety trial. This time it was licensed and I would be receiving it along with everyone else.

However, I felt frustrated because this was not the end. After vaccination, there would be more waiting. Two weeks for immunity to kick in. And then much more waiting for transmission to drop dramatically before the country could start lifting lockdown restrictions and return to anything close to normality.

I felt fine going to bed that evening, but at one in the morning I woke up feeling nauseous and freezing cold, despite winter pyjamas and a thick duvet. My feet were like blocks of ice.

I got a glass of water and some woolly socks (hand-knitted by my father), got back into bed and began to shiver violently.

If I tensed my muscles I could make the shivering stop, but as soon as I relaxed to go back to sleep it started up again. Then I began to feel very hot.

When the alarm went off at seven o’clock, I felt normal again, though weary after a broken night. I felt grateful, though. I had experienced a few hours of discomfort, but I had known what was happening and how long it was likely to last.

This was so much better than starting to experience Covid-19 symptoms and – as had already been the case for more than 100 million people – not knowing what lay in store.

Cath Green

Thursday, February 18, 2021.

Exactly one year after we had kicked off to make the starting material for the first batch of our vaccine, I was once again waiting to receive a small empty-looking tube holding 100 billion strands of DNA.

It was for the spike protein for the new South African variant, and my team would once more be making it into a vaccine.

I was, as had become the norm, worried. This time we knew a lot more about how to make the vaccine. Nonetheless, the pressures felt strangely similar to the last time. How many doses would we need? How fast could we go? Also, there were new anxieties for this year: how many more variant vaccines would we have to make?

Although it felt like an end to the pandemic could be in sight with the rapid vaccine rollout, it also felt that missteps over new variants could set us back again. I was not sure the team could take that. Our resilience was close to crumbling.

New variants are inevitable and we had expected them, but we had not, perhaps, anticipated that they would emerge quite as fast as they did. 

At our Clinical Biomanufacturing Facility, in Oxford, we had even allowed ourselves to relax a little, thinking our job with Covid-19 was done and we could start to ‘go back to normal’.

By early 2021 we knew of three variants of concern – Kent, South African and Brazilian. And by early February, we had good evidence that the vaccine still worked against the Kent variant, so we focused on the other two.

The signs were good that our vaccine would still prevent death and severe disease, but it looked like they were unlikely to do as well in preventing mild and asymptomatic cases. Later on, of course, we had to think about the Delta variant, which was even more transmissible than the Kent variant.

Happily, we didn’t have to make new vaccines from scratch. Instead we would use the methods we’d used in 2020 – we just needed the genetic code for the mutated virus.

Exactly one year after we had kicked off to make the starting material for the first batch of our vaccine, I was once again waiting to receive a small empty-looking tube holding 100 billion strands of DNA. It was for the spike protein for the new South African variant, and my team would once more be making it into a vaccine, writes Cath Green (pictured)

We also wouldn’t need to repeat all the clinical trials, since this was just a tweak of the original vaccine, and if the vaccine behaved as expected we should have a booster shot by the autumn of 2021.

One day we might be able to design one vaccine that works well against multiple variants (not forgetting that the existing vaccines do, to some extent, still work against them all). We even might be able to design pre-emptive vaccines against variants that we have not yet seen. None of these issues feel insurmountable.

The good news is that we also think it is unlikely that the virus can mutate in a way that keeps it functioning but makes our vaccine completely ineffective.

That’s because a change in the spike protein – which allows the coronavirus to enter and infect human cells – that is radical enough to make our vaccine completely ineffective would also, almost certainly, be so extreme as to make the virus non-functional. So although it feels like Groundhog Day, and although we are all exhausted and wondering when it will ever end, we are tackling the new variant situation with our teeth gritted and the fortifying knowledge that we know more about what we are doing and where we are headed.

We don’t know how many more versions of the vaccine we might be asked to make over the next year, but as global vaccination programmes get going, less coronavirus will be in circulation, making the chances of new variants decline, too.

There are also the problems caused by fake news spread around about the vaccine.

I encountered a woman on a camping trip who, when I asked (jokingly) if she thought 5G caused Covid, or that Bill Gates was using the pandemic to fit us all with microchips, had said: ‘I’m not saying there is definitely a conspiracy. But I do worry that we don’t know what they put in the vaccines: mercury and other toxic chemicals. I don’t trust them. They don’t tell us the truth.’

Taking a deep breath, I spent the next 15 minutes trying to persuade her otherwise.

‘I might not look it in my bare feet and this dress,’ I said. ‘I might not sound like it, either. But I am ‘them’. I’m the best-placed person in the world to tell you what’s in the vaccine.’

It was all very amicable, and I hope that I told her enough about me to let her see that I am not the thing she worries about: a global elite, out to win power and control.

I don’t have Bill Gates’s phone number. I don’t know how to put a nanobot tracker into a vaccine. I’m just Cath. I’m doing my best with the knowledge I have and the people I work with, and missing hugging my parents like anyone else.’

Sarah Gilbert

I don’t understand anti-vaxxers. Why should anyone be ideologically opposed to a safe and cost-effective public health measure that saves millions of lives and stops people from having to live with the long-term disabilities that can be caused by diseases such as polio and smallpox – and, it seems, Covid-19?

We don’t often come into direct contact with them, but some turned up to protest against our vaccine trials last June. They had arrived, shouted a bit and then left.

If they had watched the TV news that evening, they would have seen that only a few hundred yards away Prince William’s supportive visit to the vaccine centre was taking place. I wonder if they later kicked themselves over a missed opportunity.

Vaccine hesitancy, however, is a different matter. It is natural that people want to understand the risks and benefits of vaccines, and important that as scientists we engage with their concerns.

It’s been very common to read or hear things like ‘it feels like it’s been rushed’, or ‘I’ll take my chances with the virus, thanks’.

The fact is that nothing in life is risk-free. And so, when deciding whether to receive a vaccine, we have to determine whether the benefits outweigh the risks.

I cycle to work every day, on a route that I consider to be safe. However, a white-painted bike marks the spot where a young woman cyclist was killed in a collision with a bin lorry. It’s a poignant and sobering landmark, yet still I continue to use the same route.

For me, the benefits to my health, mood and ability to get where I want outweigh the very small risk of death. When it is icy, my risk assessment changes – I walk or drive instead. When there is snow, I walk.

With the vaccine, most side-effects are mild – a sore arm, a fever, fatigue, headache – and will have been picked up during clinical trials.

Very rare side effects might be identified only after millions have been vaccinated. This is what happened in March and April when reports started emerging of a very small number of people developing a rare type of blood clot soon after being vaccinated against Covid.

It was possible that these blood clots had been caused by the vaccine but it could not immediately be established for certain – because these events were so rare and could occur naturally even if vaccination hadn’t happened, it was very difficult to understand what was going on and why.

Both the UK and the EU regulators said that the risk-benefits were hugely in favour of continuing to use the vaccine. In the UK, alternative vaccines were being offered to adults under the age of 30, which was later changed to include the under-40s.

The reasoning was not that the risk to younger adults was higher. It was that the benefit of the vaccine to this age group, who were much less likely than older people to die from Covid-19, was lower, particularly now that there were lower case rates and alternative vaccines available.

We have proven that the UK can be a global driver of innovation and we should build on that success. If the underpinning work is done in advance, then the production of a new vaccine against Disease Y at speed would become the final flourish: the cherry on top of the cake. The problem is that people are prepared to pay for the cherry, but they won’t pay for the cake

Rare and dramatic events such as blood clots, or plane crashes, can make people worried.

Taking a vaccine is not risk-free, because nothing is.

But not taking a vaccine is also not risk-free.

You risk getting the disease yourself, and also passing it on to others. My advice is to accept a Covid-19 vaccine as soon as you are offered one. That’s what I did.

There will inevitably be more loops on the rollercoaster, more bumps in the road.

What none of us foresaw, though, was how the vaccine would become a political football.

Our year of painstaking attention to detail resulting in a vaccine with the potential to save millions of lives around the world could be dismissed by a politician with a grudge. Carefully worded statements to the media, explaining the science behind the vaccine, would disappear in a Twitter storm of bias and misinformation, with incorrect statements repeatedly cited as fact.

Certainly next time – and there will be a next time – we should add political scientists to the team.Cath Green

Disease Y – the next outbreak or pandemic – is coming. It is inevitable. Experts in animal-to-human transmission of viruses have already warned about how the trade in wildlife, and the pressures created by intensive farming on industrial scales, are creating the opportunities for it to emerge.

But just as Sarah and I didn’t know that Disease X would be a coronavirus, we don’t know what Disease Y will be.

It could be a completely unknown and unstudied virus. There are an estimated 1.67 million viruses circulating in the world, and it is thought several hundred thousand are capable of infecting people. Scientists have studied 263 of them.

Equally, there is a long list of nasty pathogens that we already know about for which we still have no vaccines or treatments. Last year, with all eyes on the Covid pandemic, there were 14 outbreaks of Crimean-Congo haemorrhagic fever across Africa, Asia and Europe (my team were working on a vaccine before it had to be delayed to focus on Covid).

There were three outbreaks of another coronavirus, MERS, in the Middle East; two of Lassa fever in West Africa; and two of Nipah in Pakistan and India.

Sarah and I have been working on projects to develop vaccines using the same technology as our Covid vaccine for both Lassa and Nipah, and with our colleague Tess Lambe we are about to start clinical trials of a new ebola vaccine, again using the same basic platform.

Thanks to the efforts of 2020, we now know we have the platforms on which to build safe and highly effective vaccines at great speed. And these can still be improved further from where they are now.

But it is possible – and it’s tough to say, after more than a million deaths – that the next time, things could be worse. It is certainly possible to envisage a future scenario in which a highly contagious and much more fatal disease appears.

So there is an enormous imperative for us to learn as much as we can from our experiences of the past year. This pandemic was not unexpected. We had been expecting it, and worrying about it, for years, but it was not properly prepared for. 

It would be terrible to have gone through everything we have all gone through and then find the economic losses mean there is still no funding for pandemic preparedness. We need to make sure that when Disease Y arrives we are better prepared than we were for X.

The solutions are not necessarily cheap or easy, but nor is dealing with a pandemic.

While we had some funding in Oxford for research and development of our vaccine technologies before 2020, we had not been able to secure funds to work on speeding up the process, or to work out how to manufacture at scale.

This work could have cut months off our response time, and the amounts we were asking for – a few million pounds – look laughably tiny compared with the hundreds of billions we have had to spend on fighting this pandemic.

It is also important to point out that a significant chunk of the UK funding that Sarah and others at Oxford University have received for vaccine development in recent years has come from the UK’s Official Development Assistance budget – a budget that has just been cut.

We have proven that the UK can be a global driver of innovation and we should build on that success. 

If the underpinning work is done in advance, then the production of a new vaccine against Disease Y at speed would become the final flourish: the cherry on top of the cake. The problem is that people are prepared to pay for the cherry, but they won’t pay for the cake.

So, what’s next for Sarah and me?

Sarah will return to the vaccine projects she was working on before Covid. Now she can use what we learned in 2020 to accelerate them. For example, might it be cost-effective, given how much flu costs the economy, to work on flu vaccine development with as much urgency as we applied to the Covid vaccine?

It would require more funding upfront and the acceptance that not everything that was tried would work, but it might be the way to make some real progress rather than continuing to limp along as we have in the past.

As for myself, I’ll continue making vaccines for my colleagues at the university (not just against viruses – we are also working on a project to tackle gonorrhoea, among others). And I want to try to get the investment to bring my facility into the 21st Century.

The dream is a new, larger facility where we can make more innovative medicines – not just vaccines but protein and gene therapies, too, to tackle cancer and blindness and lung diseases.

And not just for my Oxford colleagues but for academics across the UK. There are still a lot of diseases out there that need cures, and my team wants to help.

But first we both need some time to recover from the whirlwind of the past 18 months or so.

It has been an honour and a privilege to work on this project, but it has also taken its toll.

Andy Pollard says it has aged him ten years.

When an interviewer asked him and Sarah recently, ‘What do you look forward to doing once the pandemic is over?’, they just stared blankly at their screens, before Andy said he couldn’t remember what life used to be like. Another colleague says that he feels he has been through a traumatic experience.

I know how he feels. We have all kept going because we had to, but now we are looking forward to the ebbing away of the adrenaline and cortisol that has kept us moving all year.

Sarah needs to potter in her garden and dust off her running shoes. I need to buy a round of drinks, dance in a crowd and see my daughter hug my mum.

We both need to experience some days off without constantly checking emails.

Then, batteries recharged, we will be ready for the next challenge.

© Vaxxers Limited, 2021

Abridged and edited extract from Vaxxers by Professor Sarah Gilbert and Dr Catherine Green, published by Hodder & Stoughton on July 8 at £20. To pre-order a copy for £17, go to mailshop.co.uk/books or call 020 3308 9193 before July 11. Free delivery on orders over £20.

Source: Read Full Article