The UK is now among the nations leading the way with COVID-19 vaccination.
Last week, the Government announced that all UK adults would be offered their first dose of coronavirus vaccine before the end of July, in addition to unveiling the world’s first challenge trials, when volunteers will be infected under controlled conditions to give new insights into vaccines and treatments.
Kate Bingham, a venture capitalist, was appointed the Chair of the UK Vaccine Taskforce last May to manage the path towards the introduction of a COVID-19 vaccine. Her unpaid role, which reported to the Prime Minister, finished at the end of the year.
Her edited responses are shown in italics.
HOW DO YOU THINK THE VACCINE ROLL OUT IS GOING?
Well, it seems to be going really well. The range of healthcare workers and volunteers working on the vaccination programme is just phenomenal.
One of the reasons we signed the vaccine contracts early in July and August was to give the NHS teams as much time to prepare as possible because we knew deployment was going to be complex and difficult since it has never been done at this scale before.
All we could tell the NHS teams was which vaccines we had secured and the characteristics of those vaccines, that is cold chain, storage requirements, likely shelf life and so on, but we couldn’t tell them which vaccines were going to work, when they might get approved or how much they might get at the beginning, even though we knew what we had contracted. The exact number of doses would be dependent on ‘best efforts’ scale-up and yield so we weren’t going to be sure exactly what would be delivered. Getting those deals done early seems to have made a big difference because it looks like the NHS has been very well prepared.
I am delighted and I keep getting emails from people saying ‘My mum has just been vaccinated or my grandmother’ and it is just fantastic.
WHEN YOU WERE APPOINTED IN MAY, WHAT WERE THE BIG UNKNOWNS IN TERMS OF THE SCIENCE AND VACCINE TRIALS?
In May 2020, there were no vaccines that had ever been successfully developed against any human coronavirus (though there were some veterinarian coronavirus vaccines) so we didn’t have a template that showed how to do it.
We did know that it was a novel coronavirus and we knew what the virus looked like. We knew it caused viral pneumonia and there was human to human transmission. We also knew from the earlier outbreak of the related severe acute respiratory syndrome coronavirus (SARS-CoV-1) in 2003 that it used a receptor on human cells called ACE-2 for cellular invasion. Given the similarities, or homology, of SARS-CoV-2 and -1, it looked likely that ACE-2 was used by both viruses for cellular entry.
So, it was likely to be an infection through the respiratory tract but we didn’t know what the immune responses to the virus were, we did not know what level of immune response or ‘correlates of protection’ we had to generate with a vaccine to protect against infection and we didn’t know what triggered some people to get very severe COVID or how to identify those people and protect them.
So, the short answer is we didn’t know very much. That is also why we backed the idea of the challenge trials, which are important for the ongoing characterisation of the SARS-CoV-2 virus and how it infects people, as well as being able to evaluate next-gen vaccines and therapeutics.
In terms of the vaccine trials, the Phase 1 trials which are focused on assessing safety have been like any other Phase 1 trial, though if anything they have been bigger than normal. The Phase 2 and 3 efficacy studies again were larger than usual and were basically just compressed and done more quickly so as to get the final results as soon as possible.
For example, when Oxford published their Lancet paper in July, that described immune responses from their Phase 1/2 trial, they had already recruited 8,000 – 9,000 volunteers into their Phase 3 study. So that acceleration of the Phase 3 trial is unusual but the actual method of running the studies was no different from normal.
COULD YOU SPEED UP THE MANUFACTURING AND REGULATORY PROCESS?
There are two rate limiting steps to running clinical trials.
The first is what I generously call the bureaucracy, so getting all the ethics committee approvals and approval from the regulator, the MHRA, to start vaccination. All those regulatory bodies worked evenings and weekends to make sure the approvals got done very quickly. I wish it would always be like that. That issue was solved I would say largely for the COVID vaccines and included the MHRA launching their new process of rolling reviews, to review all the non-clinical and manufacturing etc data ahead of time and support the companies in preparing their final dossier.
The other aspect that takes a long time in clinical trials is recruiting patients, or in this case volunteers. So that’s why we set up a national citizen registry on the NHS website – the NHS Registry which has never been done before, though it should have been. To my knowledge, this has not been done anywhere else in the world. We now have 440,000 members if the UK public signed up on the NHS registry expressing interest to join clinical studies.
We were then able to say to the different vaccine companies that we had this pool of volunteers ready that they could draw on for their clinical trials. Over a third of the registry members are over 60, as we specifically enriched for those people who are at particular risk from COVID infection. We only have 8% from Black, Asian and Minority Ethnic communities versus the 13%/14% representation in the national population so we were low on ethnic diversity, despite working closely with a wide range of community leaders, religious groups and patient advocates.
The pool of volunteers proved to be a complete game changer. So, if I take Novavax as an example, a US company, we offered them support with running their Phase 3 clinical trial in the UK. They started with 10,000 volunteers in October, and then decided to expand the trial to 15,000. Yet we still finished that recruitment ahead of schedule largely because of the volunteers in the registry by the end of November. This study is now the single largest placebo-controlled vaccine study that the UK’s ever run.
And as you know, the Novavax vaccine – which is based on SARS-CoV-2 spike protein grown in moth cells – generated an 89% efficacy rate and safety and we could not have shown that so quickly without the registry. In fact, the UK finished that Phase 3 study before the US even started their Phase 3 study.
DID THE SECOND WAVE MAKE IT EASIER TO TEST VACCINES?
Yes. The challenge we had over the summer of 2020 was that lockdown had been so effective that there was very little viral transmission and very few cases. The good thing – from a clinical trial perspective of course – about everybody going back to school, work and college in September was it triggered a spike of cases in the autumn which was important for the clinical trials if we were going to able to show protection with the vaccine versus placebo quickly.
WHAT WAS YOUR OBJECTIVE WITH THE VACCINE – SAVE LIVES OR STOP TRANSMISSION?
The Prime Minister and the Chief Medical Officer Chris Whitty both said we need to stop people from dying as soon as possible. That was our primary goal. And of course, we’d like to get to a sterilizing immunity if we can, where the vaccine stops transmission, but we recognized that may not be possible with the first generation of vaccines. So, the goal was very clear. Stop people from dying by quickly finding vaccines that are safe and effective and that can be delivered to the UK ASAP.
But, of course, even then we expected variants, so part of our manufacturing plans was to make sure that we had that flexible manufacturing capability so that we could pivot and manufacture vaccines quickly as and when these new variants emerged.
HOW DID YOU KNOW WHICH VACCINES TO BACK?
It was not very different from what I do in venture capital, which is you have to look at a market and data to figure out who the different players are, the opportunities, risks, all of that stuff. It wasn’t particularly a cost issue.
Although I’m the mouthpiece of the Vaccine Taskforce, the team that I work with are off-the-charts fantastic. Between us, we had relationships with almost every single vaccine company, so it was very easy for us to pick up the phone and say we’d like to talk to you about your vaccine data and how the UK can work with you to secure vaccine supply.
Because we were quick and because we have the relationships it wasn’t a very difficult conversation actually, because they understood we would do deep due diligence which we duly did, and based on that work selected the ones we thought were most promising.
We looked at preclinical – mostly – and clinical data on their vaccines and their manufacturing capability. If we didn’t think the company could manufacture or find a way to manufacture their vaccine at scale or quickly, that knocked them out quite quickly.
Security of supply was important to give us the confidence that we were going to be able to actually get the vaccines, irrespective of what we’d agreed in the contract. In terms of the clinical data, we focused on those vaccines able to enter the clinic in 2020 because our focus was on speed.
Diversity was important so as to spread the risk of different approaches in generating protective immunity. There was a heavy focus in the first-generation vaccines on using the spike protein and delivery by injection. It was important that adjuvants – which boost the immune response – had an established safety profile. We had to believe that the clinical programmes were going to deliver quickly. We wanted to be convinced that the vaccine companies understood the MHRA’s regulatory requirements.
Cold chain stability was obviously critical, especially for the messenger RNA vaccines. Single versus two dose regimes was important, and the Johnson and Johnson/Janssen vaccine is currently the only single dose vaccine. Oxford was originally supposed to be a single dose but it turned out that a two dose vaccine regime elicited stronger immunity.
We looked at the vaccine companies’ track record of bringing products to market, albeit not all the companies that we prioritised had done that, such as Novavax and Moderna.
We basically created a blended portfolio of highly risky but more advanced vaccines and less risky but less advanced vaccines. The highly risky ones played out. No one, I think, expected them to be as successful around the globe as they have been, because mRNA vaccines (the approach used by Pfizer/BioNTech and Moderna) had not been proven in their previous trials.
I think we were successful in this global pandemic because everyone collaborated and concentrated on getting a safe and effective vaccine and invested whatever was needed to prove the safety and protective immunity of vaccines.
HOW DID YOUR TEAM WORK TOGETHER DURING THE PANDEMIC?
I had a steering group of nine – they are all superstars. Nick Elliott was the Director General who ensured that the VTF decisions made were executed – which he did flawlessly.
We had Clive Dix leading vaccine strategy including triage, due diligence and so on, Ian McCubbin leading manufacturing strategy, Divya Chadha Manec leading clinical trial strategy, Ruth Todd leading the project management and deployment working closely with the NHS teams, Tim Colley a former diplomat, leading our international strategy, Maddy McTernan leading commercial negotiation and contracting, and Steve Bates, the BioIndustry Association CEO leading long term legacy planning, all supported by Dan Osgood, our strategy director from BEIS, the Department of Business, Energy and Industrial Strategy.
I would never have thought you could have an effective team when I had not even met three of them, as in this case. But we had a common purpose. We had a very similar, completely crazy working style. I still wonder what would have been different if we had all met.
TELL ME ABOUT USING MORE DIVERSE VACCINES?
The fact is all the leading vaccine companies have focused on using the virus spike protein to induce protective immunity.
We addressed that lack of diversity by including Valneva to our portfolio, which makes a whole inactivated viral based vaccine. That vaccine format has a broader antigenic real estate beyond the spike protein, potentially generating a broader immune response. That vaccine I imagine could get used for pre winter booster injections that can address variants as well. Other than that, we did not have a portfolio beyond vaccines that used the spike because the most promising advanced vaccines didn’t have that capability.
We have to get away from minus 70-degree cold chains because that is not practical in the long term, since the cost of deploying these RNA vaccines is very substantial. The CureVac partnership, which was done after I left, looks attractive because that’s an unmodified mRNA vaccine which can be tweaked quickly to address variants, which is much more stable.
I think we should be looking at delivering vaccine by patches, nasal and through the oral route too, if you can do it. We are looking for anything that is scalable, stable and doesn’t require health care professionals and that doesn’t require massive logistics to actually vaccinate people.
WAS A UK MANUFACTURING BASE IMPORTANT?
Security of supply was definitely important both for the immediate response to the pandemic as well as to provide security of future vaccine supply against variants or new pandemic viruses. Three of the seven vaccines we ordered, and now four, if you include CureVac of the eight, are manufactured in the UK. So that is Oxford, Novavax, Valneva and now CureVac.
The Oxford vaccine is being manufactured by a network of expert manufacturing organisations including Oxford Biomedica, Cobra Biologics and Wockhardt, and the Novavax vaccine is manufactured by Teeside-based Fujifilm.
The Government funded the Cell and Gene Therapy Catapult to acquire a veterinary vaccine manufacturing plant in Braintree to make COVID-19 vaccines in a state of the art plant, which is due to open in December 2021, and this facility could be used to manufacture the Curevac vaccine for the variants. The Government also funded the upgrade of Valneva’s manufacturing plant in Scotland to enable it to manufacture whole inactivated COVID-19 vaccines, which requires very specialised containment facilities.
However, we didn’t make the UK manufacture a condition because that would have limited our ability to build the most promising vaccine portfolio. We included Pfizer/ BioNtech mRNA vaccine in our UK portfolio since that is manufactured in Europe (alongside a separate supply chain in the US) so we felt confident they could deliver. Conversely, we did not feel so confident about early delivery from Moderna despite its strong clinical and preclinical data because its primary supply chain was based in the US and the European supply chain was only going to kick in later. We judged that Pfizer BioNTech would deliver the vaccine to the UK sooner than Moderna. And that’s what played out.
DID YOU GET INVOLVED IN WORKING OUT WHO TO VACCINATE FIRST?
No. Population prioritisation was done by the Joint Committee on Vaccination and Immunisation, JCVI.
They advised us early on which were the likely populations that they would be prioritizing and that prioritisation is now public. Overall, they were aiming at the over 50-year-olds plus the younger adults with severe underlying disease. So that’s about 30 million people in the UK. That was the basis for the doses that we procured, though we got enough for the full adult population from AstraZeneca and CureVac.
WERE YOU WORRIED ABOUT VACCINE HESITANCY?
A line-up of experts, including US physician Dr Anthony Fauci and Vaccine Deployment Minister Nadhim Zahawi MP, this week discuss vaccine hesitancy, described as one of the greatest challenges facing the COVID-19 vaccine rollout, at a Science Museum online event.
Addressing vaccine hesitancy is very important as we need a high level of vaccination in the population to control the pandemic and protect those unable to take a vaccine such as the immunocompromised. While addressing vaccine hesitancy was not in the VTF’s direct remit, we did seek to get those people most at risk to participate in clinical trials through the NHS registry. One noticeable vaccine hesitant population is the BAME community.
We spent time working with community leaders and religious groups and local advocates to try and reach those groups because we have to be sure that the vaccines that were being developed actually work for the people who are most at risk. If you can persuade those at risk to join a trial, you can be pretty sure that they will ultimately take the vaccine once it is shown to be safe and effective. Effective patient advocacy has a knock-on effect, where those people who are vaccinated can go back to their communities and say ‘look I took part in this clinical trial and this is what happened.’
WERE YOU ALSO LOOKING AT THE BIGGER PICTURE, THAT OF GLOBAL VACCINATION?
That was the second of my three goals. The first goal was to protect the UK and the second goal was to ensure that any successful vaccine was distributed internationally so that anybody who needs it would have access to a safe, effective vaccine. In the contract with Astra Zeneca, international supply was part of the deal and they’ve now signed north of three billion doses in terms of supply around the world.
The UK also committed a very substantial sum of about more than half a billion pounds to the global Covax initiative to support the discovery, manufacture and fair distribution of COVID-19 vaccines for one billion people in low and middle income countries by the end of 2021.
We punched above our weight to ensure that vaccines would get to low- and middle-income countries. I am also pleased by the recent news that the UK is to give away excess doses to those countries through Covax. If we are to control this pandemic, it is critical that everyone at risk gets vaccinated no matter where they are or their ability to pay.
HOW IMPORTANT WAS THE UK SCIENCE BASE, FUNDED BY THE MEDICAL RESEARCH COUNCIL, NATIONAL INSTITUTE OF MEDICAL RESEARCH, AND WELLCOME TRUST?
Completely critical. When Government Chief Scientist Sir Patrick Vallance recommended that we needed to have a dedicated Vaccine Task Force in order to procure vaccines quickly, he said to me, ‘you’ve got to figure out your UK offer so that you can attract the companies with the most promising vaccines to come to the UK’.
The UK’s strong academic base, having very well-respected clinical regulator and national clinical trials capability were all completely central. If you add to that all the mass sequencing of virus that we have done which is critical for pandemic surveillance, we had a lot of chips in our hand. The MHRA’s long-term safety monitoring, or pharmacovigilance that allows vaccine companies to assess the performance of vaccines in the real world, in real time is also a very valuable capability. So overall the UK was able to make a pretty attractive offer.
And the reason that the manufacturing got going quickly was because of the BioIndustry Association, BIA, which is the UK trade body for the biotech sector. In February, the BIA assembled the UK’s bioprocessing community, including contract development and manufacturing companies and asked how they could help scale the Oxford vaccine from an academic scale vaccine process into a bulk industrial MHRA approved process.
They worked hard together for at least three months before any contracts were signed because they knew it was the right thing to do to get going asap. Any time delays in planning and executing the manufacturing scale up would delay the time that vaccines could be delivered – and more lives would be lost. We are very privileged to be part of a country which has such a generous and effective bioprocessing community as that made things a lot easier.
WHAT SURPRISED YOU IN THE RACE FOR THE VACCINE?
Well, personally I voted remain and I was surprised by the difficulties of trying to work with the EU- it never occurred to me that the vaccine wasn’t something that we would all work on and contribute to together since this isn’t a political issue as such.
But the European Commission was clear that they wanted to impose significant restrictions as to what the UK could do if we joined their procurement process and I did not see why it was in anyone’s interest to accept those restrictions. I suspect the EU would probably be working in a different, more collaborative way with the UK if we were doing it again knowing what we know now.
WHAT WAS THE HIGH POINT OF THE RACE FOR THE VACCINE FOR YOU?
One high point was being part of the Novavax trial and then getting the data to show how positive the vaccine results were. Based on our due diligence, I really liked that vaccine because it’s a more established format, using a formulation of virus spike protein with adjuvant delivered in virus-like particles, VLPs, and the preclinical data looked very good.
Though I’ve been funding companies and running or funding clinical trials for nearly 30 years, I’ve never taken part in a clinical trial. So, it was very interesting to actually be a trialist. I still don’t know if I got the vaccine or placebo, but seeing the data in January, which showed almost 90 per cent efficacy, was absolutely the coolest moment ever.
Another great highlight was how the pandemic has triggered real interest in science from both students and the public. As I’m particularly keen to encourage more women to study and work across all fields of science – especially getting schoolgirls engaged – this interest in how science can translate in real time into saving lives is very exciting.
HOW CAN I FIND OUT MORE?
There is more information in my earlier blog posts (including in German by focusTerra, ETH Zürich, with additional information on Switzerland), from the UK Research and Innovation, UKRI, the EU, US Centers for Disease Control, WHO, on this COVID-19 portal and Our World in Data.