Andrew Pollard: The Oxford-AstraZeneca vaccine

Andrew Pollard provides fascinating insight into the Oxford-AstraZeneca vaccine during the Covid pandemic given his central role in its clinical development, explaining how experience with past coronaviruses left his team well placed...

Chris – All this must have been like a massive dose of steroids once Covid came, because the committee must have been used to making decisions at a much slower pace. It’s not often that new vaccines come along and have to be evaluated, and so all of a sudden you were confronted with making decisions about a whole new disease, whole new groups of the population who might need to be protected, with a whole new slew of different vaccines all coming along all at once.

Andrew – Well, the first thing to say is that the committee does review new vaccines every year – it's the bread and butter. We're often re-evaluating the current schedule and perhaps reducing the number of doses because new evidence emerges that protection is sufficient. Sometimes we find that you need extra doses, and the wonderful surveillance system we have in the UK allows us to do that. When it came to the pandemic, I was working on the Oxford-AstraZeneca vaccine and the clinical development of it, so I actually stepped back from chairing the Covid committee for the JCVI during the pandemic. My colleague Wei-Shen Lim took over that role in order to make those decisions, and they really did work very hard, with meetings often several times a week, to review that huge deluge of data and new information being provided.

Chris – But we got the impression – I mean I'm talking in terms of the general public seeing this – we got the impression that the government were asking committees like the JCVI to make really important decisions about things like, well, do we give Covid jabs to kids? And almost justifying what the political position was going to be based on what the JCVI was saying. But you were operating with very, very limited data.

Andrew – Well, as I said, I wasn't involved myself directly in that decision-making, but I think one really important thing in policy decisions during such a situation is that you have to make decisions. The data are almost always incomplete, but if you do nothing, it results in people dying. So the decision-making has to be based on the best evidence available at the time. And always with programmes like this in an emergency, you're constantly reviewing and revising your decision-making depending on new information as it comes.

Chris – Did we learn a huge amount about how to conduct trials at scale, do it very quickly and make decisions very quickly, or did we go too fast, do you think? Because it really surprised everyone when all this started and we were told, well, normally it takes years to get a new drug even out of a test tube and into a person's arm, and then to do all the trials and get the approvals and so on. A decade's work was effectively condensed into – you know – ten years became ten months, almost, didn’t it? So what have been the learning points from the pandemic that have now improved and streamlined how we do this sort of thing?

Andrew – I would look at it slightly differently. I would say that we already knew a lot about coronaviruses, and because there had been small outbreaks over the 20 years prior to the COVID-19 pandemic, we already knew how to make the vaccine. There was an outbreak of the original SARS virus – severe acute respiratory syndrome virus – in 2001, and then the Middle East respiratory syndrome virus in around 2012, and those were pretty awful infections.

The first one killed about 10% of those infected, and the second epidemic about 30%. So that really focused efforts on understanding how to make a vaccine for coronaviruses. So when 2020 came, we didn’t need decades of research – we already knew exactly what to do to make a vaccine. All we had to do was that last sprint to the finishing line over that nine to eleven-month period in order to have a vaccine ready for licensure. The only bit we were doing was the clinical development – to show that in a large number of people, in our case about 25,000, the vaccine was safe and efficacious.

The reason why that bit could be done quickly was simply that you didn’t have to wait for someone to pay for each of the next steps. Normally, that process takes years just because you complete one stage, and then spend a year or two trying to find funding for the next bit. But during the pandemic, we had the money – or at least, we had to beg for it, but we got it – to run the trials and get the data to submit to regulators.

Chris – The vaccine that you helped to develop – the Oxford vaccine that then became more widely known as the Oxford-AstraZeneca vaccine – that actually is the sort of backbone technology that has been redeployed in various directions, hasn’t it? Because you've used it in a range of different disease contexts. Ebola benefited from that backbone, didn’t it, as well?
Am I right in saying that?

Andrew – Yes. The viral vector – this is adenoviruses. One of the Ebola vaccines uses a different adenovirus, an adenovirus type 26, which is the product produced by Janssen or Johnson & Johnson, who are now the parent company. We used a slightly different adenovirus from chimpanzees, called ChAdOx, for our vaccine backbone.

Chris – But basically, to make a long story short, it’s a virus that acts as a Trojan horse. It takes into the body a bit of the coronavirus that you want to persuade the immune system to recognise.

Andrew – Well, it actually takes the gene from a bit of the coronavirus, and then our cells make that bit of the coronavirus. So we’re using our own cells as a factory to generate the vaccine, which we then develop an immune response against.

Chris – How did AstraZeneca get involved? Because you had that technology, you were already working on it. So how did it end up being the AstraZeneca-Oxford tie-up?

Andrew – Well, what we know how to do in Oxford is design vaccines and conduct clinical development. But we're not a global pharmaceutical company – we're a university. What we really needed was a partner with expertise in manufacturing and distribution on a massive scale. AstraZeneca brought incredible expertise in that global space. They took on over 20 manufacturing sites to protect manufacturing across different world regions from nationalism. And they distributed those doses to the countries and geographies where the vaccine was needed.

Chris – It was done at cost though, wasn’t it? That was another attraction. Or was that the insistence of your team in Oxford – that they do this at a scale that wouldn't end up breaking the bank for countries that otherwise might not be able to afford vaccines?

Andrew – AstraZeneca was chosen as the partner because they were prepared to distribute the vaccine not for profit. For the university, this was very important – in a pandemic, there should be no perverse incentive to sell only to rich countries. Because there’s no profit involved, it doesn’t really matter whether you're going to low-income settings, middle-income countries or high-income countries. The point is to get it to those most at risk – which, of course, are the elderly in any population.

Chris – What about the risk to the company though? Because this is AstraZeneca in 2020. Were they, in their view, taking a big risk in taking on the technology in an untried, untested way, apart from the initial trials that had been done?

Were they worried about their reputation? Were there conversations around what could happen, and what safeguards were needed to protect the reputations of you at Oxford, AstraZeneca, and the public?

Andrew – I think the discussions about taking this on were, firstly, grounded in a strong view from AstraZeneca's leadership that there was a moral obligation. They had capabilities we didn’t have, and this was an opportunity to use those skills for the public good during a pandemic. There’s also a commercial argument: if you're able to contribute to ending a pandemic earlier, that benefits the entire business environment.

So, there’s good logic in using the resources and expertise of the company to help get the world back on its feet faster – which in turn allows them to return to their core business sooner.