INTERVIEW

‘We should forget about herd immunity. It’s the wrong concept, because of the variants’

Andrew Pollard, the director of the Oxford Vaccine Group and the man who led the clinical trials for the AstraZeneca vaccine, believes that new strains of the coronavirus will find ways of transmitting and causing mild infections

Professor Andrew Pollard, the director of the Oxford Vaccines Group, in a photo supplied by the university.
Professor Andrew Pollard, the director of the Oxford Vaccines Group, in a photo supplied by the university.

Andrew Pollard is well aware of the turbulent time that the Oxford-AstraZeneca Covid-19 vaccine has had. The 55-year-old director of the Oxford Vaccine Group at the English university was at the forefront of the medication’s clinical trials in the race to defeat the coronavirus. His vision of everything that happened is sufficiently neutral and distanced for him to still be convinced that the AstraZeneca vaccine will have a relevant role to play in the coming years, despite its association with very rare episodes of blood clots that have been detected in a small number of people vaccinated with it. But that has not stopped him from recognizing that, as some governments have decided – among them, that of Spain – that the alternative of combining vaccine doses from different manufacturers is safe and effective. Pollard points out that in many parts of the world, unlike in Europe, the war against the virus has barely started. He also rejects the idea that we should be talking about herd immunity. The new variants of the virus, which are constantly appearing, will make this impossible to achieve. For this interview, which has been edited for length and clarity, Pollard spoke to a small number of media outlets from the LENA European alliance, of which EL PAÍS is a member.

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Question. There have been some media reports citing a new study that confirms the AstraZeneca vaccine works well as a booster. Will we need a third dose next autumn?

Answer. At the moment, we don’t know if we need booster doses of the vaccine. I mean, that’s something which will become apparent in time. We do think that all of the vaccines that are being used here in Europe at the moment are giving fantastic protection against Covid-19. And so, the question really about booster doses is two things. One is, will the immune response wane over time? Will people actually need boosting to maintain that protection? We don’t know the answer to that yet. We haven’t had enough time to fully address that question. And the second possibility is, could the new variants, as they emerge – and they’ll continue to do that over the years ahead – find their way around the immune response that’s generated by the vaccines that we have at the moment?

For both questions, we have strategies. We could boost people with further doses, or we could use new variant vaccines, which focus more on variants that emerge over time.

Q. How worried should we be about the Indian variant of the virus and the effectiveness of the current vaccines against it?

A. Well, I think that focusing on the Indian variant is perhaps the wrong thing to do, because it is just one of many variants which are going to appear in the months ahead. So the question really is whether the vaccines that we have, the programs that we have at the moment, are going to be sufficient to keep people out of hospital, with the different variants which will emerge over time. I think the evidence we have so far is quite reassuring. With really severe disease, the vaccines are going to remain highly effective, even with new variants. However, the whole point of the virus throwing up new variants is to continue transmitting on veteran populations. And that will include vaccinated populations. So, I think future variants will find ways of transmitting and causing those mild infections, mild disease, even asymptomatic infection.

As always in pandemics it’s an evolving story. Everything looks very promising at the moment. We are just a little bit early to have certainty

I wouldn’t worry in that sense. The real question is the one that we haven’t quite got an update from, which is the certainty that the vaccines, at the moment, will just stop people from going into hospital, at least the majority. But it’s probably a very short time to have that answer. Now that the variant that was first identified in India is spreading here in the UK and in other countries, we’ll start to get an idea very quickly about whether the vaccines that have been used are sufficient to stop people getting into hospital.

So as always in pandemics it’s an evolving story. Everything looks very promising at the moment. We are just a little bit early to have certainty.

Q. Is it inevitable that we will have to vaccinate the whole population on a yearly basis against Covid?

A. I don’t think it’s inevitable yet, we just don’t know. It’s not the same virus as influenza, where everyone is thinking about the flu virus and how that behaves and how it changes every year. Coronavirus is very common in human populations. All of us on this call would have been infected by coronaviruses as children. And what happens when we become adults is that we still get mild infections with them. Perhaps last year, when you had a cold, that was caused by coronavirus.

So despite having immunity from childhood infection, we still get mild infections during adulthood. It could be that with the vaccine program that’s in place, most people will have enough protection in future years. They would only get very, very mild infections and be able to carry on without boosters. I’m speculating, based on the evidence that we have from other viruses. And I think we should be cautious and not say at this moment that we know what the future is like. We have not seen the full behavior of this virus and what it looks like, once we’ve got large parts of the adult population immunized.

Q. There is an urgent debate going on in some countries, in Spain specifically, about the effectiveness and safety of combining two different vaccines. Can the population be reassured that this is not a problem?

A. What I think, from the perspective of the biology, is: can you make an immune response by mixing schedules? The answer is that all of the vaccines that we’re using in Europe lead to immune responses being generated against the spike protein of the coronavirus. And so, if you expose the immune system, despite approaching it with one vaccine and then with another vaccine, the immune system will make a response. So, I don’t think there’s any question, from the biology of it, not resulting in good immunity.

What we don’t know is what’s the best way round to do it. How do you get the best out of a combination? Which would be the best to have first, and which would be best to have second? And that’s why the studies are needed to try and address how to optimize mixing schedules, if that’s the decision that’s made. So, from the biology, I would be certain that there would be good immune responses. But what’s the best? Is it better to have two of the same or two different ones?

We don’t have sufficient data yet with adequate controls in order to answer that question. And that’s what the ComCOV study will answer in the next month or two [Oxford University is currently carrying out research into the combination of vaccines].

But there’s a second issue, which is about how well it’s tolerated. And the results, which were released a week ago, show that at least in older adults, when you do a mixed schedule, they tend to have rather more reactions in the first couple of days after they’ve been vaccinated. Now, that can be managed and people can have that explained to them. We don’t fully know why that is, but people do feel a bit more unwell with their second dose if you use a mixed schedule. The other point here is that, in younger people, we know that, in general, with all vaccines, they have more short-term side effects. But we haven’t got a study yet in these mixed schedules. And so, it could be that there’d be slightly worse side effects or even worse in younger adults. And that needs addressing and communicating well to the public when those sorts of mixed schedules are rolled out.

Q. Would that mean that it’s not the right time to make that decision yet?

A. I think it would be good to have the evidence generated. And I think there is some recent data from Spain. [The Carlos III University Health Institute concluded this week, based on a preliminary study, that combining doses of Pfizer and AstraZeneca vaccines is safe and efficient.] I haven’t seen the full data that lies behind that report. So it’s difficult to comment on it. But that would support what I’ve said, that you can see good immune responses. But as I said, I haven’t seen the full data set.

I think we’re getting to the point where we understand something about the local reactions and the fever and the joint pains, the things people suffer when they have a second dose. So that can be communicated. And we’ve got some early evidence about the immune response, but it’s always better to have more data and there will be some more emerging in the next month or so.

Q. The authorities in Germany have announced that from June 7 priority lists will be lifted. Anyone can tell his or her doctor to give someone else the AstraZeneca dose that they had booked. Is that a good idea epidemiologically?

A. I think it’s not dangerous to lift the priority list. But the most important thing is to come back to the question of what we are trying to do with our vaccine program. Why do we have a pandemic? We have a pandemic because people are going into hospital putting huge pressures on our health systems. And in fact, we’re all living in countries where we’ve seen that happen over the course of the last year, with terrible admission rates into hospitals, and the system almost at the point of collapse, because of the number of patients.

So, if that wasn’t happening, if we could stop that happening, then there would be no pandemic. This is a pandemic because of the pressure on the health system. And the only way you stop that pressure on the health system is by focusing the doses that you have on older adults. And that’s largely the over-50s, and on younger people who’ve got health conditions.

The number-one priority is to stop people going into hospital and dying. And that’s the over-50s and those with health conditions

That priority is how we end the pandemic. So my view would be that that’s the most important thing to do in order to be able to get our lives more back to normal. Clearly, to stop new variants arising and to reduce the overall concerns that there are about the virus, having wider immunization in the population reduces transmission, and reduces the chance of someone vulnerable getting infected. Those are good things to do next. But the number-one priority is to stop people going into hospital and dying. And that’s the over-50s and those with health conditions. I’m not sure I fully answered your question, but, you know, for the individual, you should definitely have whichever dose you’re offered because that’s the way to be protected. And from a population perspective the priority groups have to come first if we want our livelihoods and our economies to get back to normal.

Q. One of the things some governments are proposing is to let the patient decide, with written consent, if he or she wants to retain AstraZeneca as a second dose instead of having the new vaccine proposed. How ethical, as a health policy, is handing that decision to the patient?

A. Well, I think clearly every country has to make its own decisions about how best to manage the population, the relationship of governments with populations, and the supply of vaccines. I think the approach taken here in the UK has been to try to have consistent communication. Like many places in Europe, we have relatively limited supplies of vaccines. And so, the approach has been trying to make sure that the program is optimized, through the priority groups, first of all. And while we didn’t have data on mixing and matching schedules, to focus on giving the same vaccine twice. But it does say in our guidance, here in the UK, that if you don’t have supply of an alternative vaccine, and someone is due their visit, rather than sending them away, you can give them the alternative vaccine. That doesn’t happen very often, because the program was quite well organized. Of course, in much of the rest of the world, there isn’t that luxury of thinking about either the patient choice, or to have things well organized to make sure you get both doses. And of course, the crisis in the world today is that for most countries it is difficult even to get the first dose, let alone to find the second dose. Many countries I’m dealing with are asking questions like, “We’ve been giving our first doses. How long can we wait for the second dose? There’s no supply.” And so I think in some ways the tragedy of this discussion is the thought that there are vaccine doses not used while people who are at high risk of dying in other countries have no access.

Q. You have recently said that is morally wrong to keep doses here, in the Western countries, instead of sending them to countries that have none.

A. I think we have to look at all of our populations, not in the nationalistic way – and I think that has happened quite a bit over the course of the last year – but to remember that we’re all part of a very interconnected global population and we know, without any doubt, from more than a year on, who the vulnerable people are, who is a high risk of dying. We’ve seen this appalling spread of the virus across South Asia, there’s a huge increase as you move further east into Malaysia, and across Latin America. Rather like Europe was a couple of months ago. We’re seeing exactly that play out in other countries. Very much so, across our nations, increasingly, we have actually vaccinated those older adults. And so, what we’re doing, if we decide, as some countries are, to vaccinate very young adults or even children, those doses are very unlikely to make a difference to survival of those individuals or to the pressures on the health system.

We really ought to be valuing the lives of those older adults in all of those other countries, before we give the vaccine to very young people who have almost no risk

And as part of an interconnected community, we really ought to be valuing the lives of those older adults in all of those other countries, before we give it to very young people who have almost no risk. I think this is the moral argument. That if you’ve got someone up near to zero risk of disease, it makes much more sense to protect the individual who’s at very high risk. But there are other arguments as well. One of the reasons why we worry about B.1617.2, the Indian variant, is because it appears to have a lot of transmission. And so, if in these many populations around the world we could contain the virus more and reduce the amount of spread, we would be less threatened ourselves. Because at the moment there are many countries where there’s huge rates of disease, there’s no vaccine, and new variants are going to come back to Europe in the future.

I think there’s a health security reason for sharing doses as well. And then the third one, and perhaps as important for politicians, is the economic argument. We clearly want to defend our own economies, but we can’t trade with other partners around the world if their economies are in collapse because of waves of the pandemic. So I think we’ve got these three arguments: the moral argument, the health security and the economy, which is why we really must share doses.

Q. The US government has announced the decision to waive vaccine patents. Oxford and AstraZeneca decided to run an alliance on a non-profit basis during the pandemic. What are your thoughts about the idea of patent waiving?

A. Well, I think it’s a great question and it’s clearly one which is a really hot topic at the moment. I think the idea behind waiving patents makes absolute sense. The idea is that you waive patents and, by doing that, you can then share the intellectual property to have manufacturing sites all over the world, increase capacity of manufacturing and then be able to save more lives. That is absolutely the right goal. And I think everyone shares that. The difficulty with that approach is that we’ve already got commercial interests which will make that difficult to achieve.

And we’ve seen political differences. Different countries have already come out strongly, one in favor or against, which already tells you that it’s going to take some time to work through that issue. But I hope that this will be dealt with, because we really need to work out a good model of some form of sharing of intellectual property. To allow wider vaccine production would be good. But if you do achieve that, you then have somewhere between six and 12 months to get new sites up and running, licensed, and to understand the processes required to make the doses.

And that is a very complex process. You need very experienced engineers, people who know about manufacturing, to help all of those other sites to learn the technology. And I think that often, when people come up with these ideas, they have not fully understood how difficult it is to make vaccines. This is not like the making of drugs, which are essentially chemicals. These are complex biological materials that are really difficult to make.

And all of the manufacturers will have some batches that fail, and they’ll have to throw away millions of doses because they don’t pass the requirements. So this gives you an idea of how complex it is. And then one of the difficulties in Europe is supply. It’s not because people aren’t trying hard enough, but because it’s so hard to make large-scale numbers of doses. And this is with companies like Pfizer and AstraZeneca, who have spent a year now trying to get supply up to the levels that we’re talking about.

So if you imagine starting today with getting other manufacturing sites everywhere to get going, in a year’s time, we will have really good supply from them. But it’s not going to fix the problem today. During this month, almost a million people will die in the world from coronavirus, and there’s no way that the IP [Intellectual Property] change will fix that. So to me, that’s the problem with the IP way. But it’s something we need to do. We need doses in 2022 for the people who still won’t be vaccinated even by that stage. But it’s not going to fix the problem today of the other people who are going to die in the next month. So that’s why I come back to how this can be worked out. How do you manage the surplus of supplies that we know exist in some countries and how do you redistribute doses that might be going to very young adults or children, for example, to make sure they’re prioritized to those who are most in need?

Now, the approach that we took from the university and with AstraZeneca last year, and I think it’s one of the things that we’re really proud of, is a deal with AstraZeneca that meant that the vaccine is distributed not for profit. So that essentially already achieved part of the aim of the intellectual property waiver, and the second part of the IP waiver that you want to achieve is distributed manufacturing. And AstraZeneca has done that. It set up more than 20 sites around the world. So that’s more than any other developer. And the AstraZeneca engineers are working with all of these sites around the clock to try to get the amounts of vaccine being produced up to the maximum yield, so that more doses can be made and to save lives. So I think in some ways, by that deal that the university did, and I think the very great vision of AstraZeneca to be prepared to come into a partnership, not for profit, has essentially achieved what we would be able to do through the IP waiver, without having to cross that difficult commercial threshold of giving up IP.

Q. You are aware of how frightened some people are about these rare episodes of clots on some patients after the first AstraZeneca dose. Do we know anything more about that possible link?

A. Well, there’s a huge amount of work going on by the regulators and by public health agencies both to understand this condition, this incredibly rare event. But also, that if it does occur, to work out how best those patients can be managed, to make sure they have a good outcome. I think the combination of those two things and making sure the public are more aware of what the risks are has really made a big difference to the perception in many countries. Where we are at the moment is that there is this incredibly rare association between vaccination with some of the vaccines, including ours, and this very rare type of clot. It is not just routine clots that you commonly get, but a very rare type.

Herd immunity for the original strain last year would have been possible. But we’re now dealing with different variants, which will continue to emerge and transmit in vaccinated populations

But there are many other things that here in Europe are much more dangerous. And I don’t know if you will be getting in your car today, but driving on the roads in Europe is far more dangerous this year than it is to get a clot from this vaccine. I think that this gives an idea of our perception of risk and that we’re prepared to get in the car and drive somewhere where there is a risk of even death, which is greater than the risk of getting these clots. And, on the other hand, it’s quite right that in some countries, including here in the UK, where there’s a supply of alternative vaccines, for younger people, where the risk benefit between the risk of Covid, which is what we’re trying to prevent, and the risk of these clots becomes finely balanced at a time when there’s not much virus around, then, alternative vaccines are being used. But if you’re in a country where there’s a lot of transmission of Covid, the risk of Covid is so great that whatever age you are, you should be vaccinated, because denying the vaccine because of a potential risk is a much more dangerous situation.

And so that’s a very confusing story for people in many countries, that it’s so much dependent on where you are on the vaccine program, where you are in the waves of the epidemic, to determine what is the best policy. It really needs a very steady hand from political and public health leaders to communicate that to the population.

Q. What would be a fair rate to say we have reached herd immunity?

A. If we were dealing with a virus that doesn’t change, then the mathematicians could work out what proportion of the population has to be vaccinated in order to stop the virus in its tracks. So, herd immunity is when you can really stop circulation just by vaccinating enough people. We know for measles that you need over 95% of people vaccinated. For some other viruses, it may only be 80% or 75%.

But for this virus, it is changing. So herd immunity for the original strain last year would have been possible. But we’re now dealing with different variants, which will continue to emerge and transmit in vaccinated populations. I think we should forget herd immunity. It’s the wrong concept because of the variants. The virus will find ways of transmitting in immune populations. In a sense, the real question is what proportion of people need to be vaccinated, that will minimize the number of people going to the hospital, or maybe even stop it completely. I think it is actually a very high proportion of the population who are at risk and need to be vaccinated. And the difficulty is that even if you vaccinated everyone over the age of 50, that will stop 99% of the hospitalizations. But then, if we give up at that point, then younger adults, the under-50s, will still get the disease. And because there’s so many of them in all of our countries, some of those people will be vulnerable and will go into hospital.

It is a difficult one balancing the requirement to try to minimize hospitalizations. Once you’ve vaccinated the over-50s, the next step in programs, hopefully when most of the world is protected, is going to be to start to vaccinate wider in the under-50s.

When you think about where we were on January 1, I think it is an amazing achievement in all countries in Europe to be looking at by this summer for the vast majority of those at risk to be protected. It’s a huge achievement.

Q. At some point, during the row between the EU and AstraZeneca, the discussion turned on which technology was best, the RNA developed by Pfizer or Moderna, or the viral vector technology used by AstraZeneca.

A. I think the RNA technologies like Pfizer or Moderna are very exciting new technologies. And I think they are going to be another vaccine platform that is going to be incredibly useful in the future. Both for diseases that we have at the moment, that we can do with improved vaccines for, and also for future pandemic threats. But one of the real successes in this pandemic is having a wide portfolio of vaccines. We’ve got RNA, we’ve got viral vectors, we’ve got protein vaccines, and we’ve got the inactivated vaccines, which are coming from China at the moment, but there are some other companies, including a French company, who will be in that space before long. And that is incredibly important for our safety in the future, to have a wide range. A year ago, we didn’t know whether any of these vaccines would work or which platform of technology would be the right one. And we’re lucky that a number of these have come forward already. But remember, there’s around 200 developers and we’re certainly not at this moment seeing 200 vaccines available on the market. So, you have to have a broad range of development. We can’t put all of our efforts in one type of vaccine or even in one developer. And of course, we’ve seen a number of developers fail, including some of the big pharmaceutical companies whose vaccines did not go well, like Merck, for example, in the US. They had two vaccines that didn’t induce good immune responses. And as a partnership between Sanofi Pasteur and GSK, they have some problems with their development and they are now hoping that they’ll have a vaccine by the end of this year.

If you focus on only one technology, I think we put the world at risk. That’s not to say that RNA is not exciting, it’s really exciting

And I think that none of this is a surprise to me because it’s really hard to make vaccines. And I think the wrong thing to do would be to be restrictive in the future, not least because if this had been some different organism, maybe not this coronavirus where we all knew what to do, it could be that the type of technologies, maybe RNA vaccines and viral vectors would have been the wrong technology. Maybe we’d have to have protein vaccines.

And if you focus on only one technology, I think we put the world at risk. That’s not to say that RNA is not exciting, it’s really exciting.

Q. Could you say we are winning against this virus?

A. I think we’re making huge progress. And you could look at individual countries and you can see this battle is slowly being won. But from a global perspective, we know we’ve just started the war. I mean, it’s got so far to go still, but it’s a very worrying situation. It feels in Europe as if we can see light at the end of the tunnel. But if you’re sitting in Nepal today or you’re in some parts of India, it just seems like this is never going to end.

So, I think we have to keep coming back to taking a global perspective and to have responsibility ourselves from a global perspective in the way that we need to be more outward looking now that we’re getting slightly ahead of the curve.

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