An interview with Sarah Gilbert

An interview with Prof. Sarah Gilbert

Content from The Andrew Marr Show, BBC, 19^th April 2020

Can we guarantee that a workable vaccine will be produced?

SG: Nobody can be absolutely sure it’s possible to produce a successful vaccine, that’s why we have to do trials to find out. I think the prospects are very good but, clearly, it’s not completely certain.

To get the vaccine to a stage where it is absolutely safe, you have to do a lot of trials which takes a lot of time. Where in that process have you got to?

SG: We haven’t immunised anybody yet. We hope to start clinical trials at the end of next week. We are waiting for the final safety tests to be completed with the vaccine and the final approvals to be given. In the meantime, we’ve been given permission to start recruiting volunteers and explaining the process of the vaccine trial to them, and to start taking blood samples from them, to check their health status before we recruit them. This means that, by the time we have all the approvals for the vaccine ready, we should have a good pool of volunteers to draw from and we should be able to get going quite quickly.

If all that goes well, when might it be ready?

SG: Well it depends what you mean by ready. There are a lot of complex stages in vaccine development. First of all, we have to immunise healthy people between the ages of 18 and 55, and we’re looking at the safety of the vaccine as we go. We have used this type of vaccine many times before so we’re not expecting any surprises. It has a very well characterized profile of what happens to people after vaccination. They may have a sore arm, maybe a slight fever for a day or two, but that’s all that is expected.

We will then increasingly immunise more people, and we’ll start to look at the safety and the immune response to the vaccine in older people as well as younger people. This is particularly important because it’s the older population that we really need to protect with a vaccine, but with vaccines in general you often get a lower immune response as the immune system ages. So, we need to find out how well this vaccine works in older people compared to younger people by measuring the immune response to the vaccination.

We will also be looking to see if the vaccine works to protect people and stops them getting infected with the virus. The way we do assess this is by giving half the people in the trial the coronavirus vaccine and half of them another vaccine – a vaccine that’s licensed to protect against meningitis. People don’t know which vaccine they’re having, and over time as people become infected or have symptoms of coronavirus, they’ll come to us to get tested.

When enough people have become positive for the coronavirus, the statisticians will look at which groups those people are in, to find out whether they are in the group that had the coronavirus vaccine, or whether all positive cases are in the group that had the meningitis vaccine.

We’re hoping for the infections to happen only in the meningitis vaccine group. And if that’s the case we will then be able to say that this vaccine works, at least in the age range we have vaccinated, and we can then start expanding the studies and we can start to apply for emergency use licensure so that the vaccine can be used more widely.

It sounds unlikely that the vaccine will be ready until around the end of the year.

SG: It’s very difficult to predict, and there are two parts to that. One is demonstrating that the vaccine works, and that will be affected by how much vaccine transmission there is at the time we’re doing the testing. Obviously, we’re seeing a drop in hospital admissions now, probably a drop in virus transmission in the community, and that’s great for the population as a whole. It makes vaccine testing more difficult though, because we need a small number of people to become infected – and it is really a very small number – in order to know that the vaccine is actually working.

We need a situation in which some people could have been infected but they weren’t, and other people who had the other vaccine were infected. So that might take a long time if there’s not very much virus transmission.

The other part is having enough vaccine ready to use. So, in parallel with the clinical trials what we need to do is start preparing to manufacture large amounts of the vaccine.

People are talking about millions of doses potentially being available by this autumn. What do you need from the government to ensure that happens?

SG: There aren’t any manufacturing facilities in this country that at the moment can make very large amounts of the vaccine. We have a pilot plant in the University that can make small numbers of doses and that’s what we’re using for the first clinical trials. But we need to go to a much bigger scale. So those companies need to have new equipment, they need to have their staff trained in using new protocols and new quality control assessments. And all of that can happen – but the companies that we’re going to be working with will need to stop doing their usual work and make this vaccine instead. So, we need support for them all to make sure that that’s done in a fair way while they’re trying to do something that’s really very important.

We are looking to protect people’s health, and to do that as widely as possible across the world. It’s not just for this country. We need to make enough vaccine for the world. And there are discussions going on about mechanisms for ensuring fair access to all the vaccines that work at a global level, which we will need to engage with.

For the moment what we’re concentrating on is getting lots of vaccine available -provided that it does actually work and will protect people. We also want to look at the assessment of other vaccines which are in development because it’s my belief that quite a number of the vaccines in development will work, and they’ll use different manufacturing facilities and that’s another way of getting lots of vaccines available for lots of people.

Do you think the vaccine will be available in Britain first?

SG: At this moment I couldn’t say where it will be available. We’re still at a very early stage in the process, we haven’t vaccinated a single person yet. And we’ve had to work very quickly to go through many of the stages of vaccine development that would normally take about five years and we’ve done them in four months… So the thinking about how we’re going to use the doses when we actually have them, when we have a vaccine we know the efficacy of, is something that’s really still to come. We’re concentrating on the clinical trials and accelerating the manufacturing at the moment.

From what you know at the moment, is it possible to be re-infected after you’ve been infected by coronavirus?

SG: Well, we can’t say for certain with this particular coronavirus. But from what we know about other coronaviruses that infect humans and infect animals, we know that immunity isn’t very long-lived. So, I think that it probably is likely that if somebody has been infected, they will be able to be re-infected in the future. We don’t know at what interval yet, possibly a number of years.

So, this is a vaccine you’d have to use again, like a flu vaccine, you’d have to go every winter and get it again?

SG: There’s a difference between immunity acquired after natural infection and immunity acquired after vaccination, they’re not necessarily the same thing. Coronaviruses are very good at not leaving a strong immune memory behind them, that’s why people get re-infected. But we’re not using the coronavirus itself as the vaccine, we’re using a different virus to make a vaccine, and with the adenovirus that we’re using, you get strong immune responses and they stay at a high level for a long period of time.

We could be in a situation, which would be very fortunate, where we could find that the vaccine-induced immunity lasts a lot longer than the infection-induced immunity.

How long do you think – and maybe this is an impossible question – the vaccine-induced immunity might last?

SG: Well, it is an impossible question. What we’ve done in clinical trials of our MERS coronavirus vaccine is looked at people’s immune responses a year after we vaccinated them and they’re still very strong then. We don’t know how strong they need to be to protect people from infection, so there’s a lot still to know, but we do know that with vaccination we get immune responses at a good strong level for at least a year.

Are you of the view that this is a single strain of coronavirus, this one? Or is it mutating around the world? Are there different strains?

SG: There are some mutations going on but not at a level that will affect our ability to vaccinate against it. In our MERS coronavirus trials we took the serum from people who’d been immunised, from their blood, and we tested it against lots of different MERS coronaviruses isolated in different years from humans and from camels, and in different countries. The serum antibodies worked against all of them, because the differences are really quite minor.

For some viruses, like flu, there’s a lot of change from year to year and between the avian viruses and the human viruses. For the coronaviruses, within one type, such as either MERS or SARS, or the novel coronavirus, although it changes a little bit as it passes through people it’s really not very much.

The World Health Organisation (WHO) has suggested there might be five or six, or even more, waves of this still to come.

SG: Well yes, because that’s what happens when people get infected and then lose immunity and become susceptible again and can be re-infected. I think it’s going to go on for quite a long time. We need to work out which vaccines are going to work to stop that and to really get this under control.

Can you explain why some people, for instance older people – men in particular – are more vulnerable than others?

SG: That seems to be largely to do with the level of expression of the receptor that the virus uses to get into cells. So, it’s the ACE2 protein that’s found on the surface of cells in the respiratory tract and the virus catches on to that and then uses it to pull itself inside the cell. We know that in children who have mild infections, they have quite low levels of ACE2 receptor expression in the respiratory tract. But it increases with age, and it’s higher in men than in women, and that seems to be the main difference in why men are having worse infections than women, and more fatalities.

And the other thing is the immune system: as the immune system ages, it’s less able to fight off viruses. As we get older, we don’t always have the capability to deal with viruses, particularly if there’s a very high viral load at the time of infection. So, if we get a high exposure to the virus, it can overwhelm the immune system and mean that we can’t fight it off. There are lots and lots of variables to be taken into account.