Covid vaccine trial on pause

To reflect on the AstraZeneca Covid vaccine trial pause, Chris Smith is joined by Cambridge University immunologist Clare Bryant, space journalist Richard Hollingham and space scientist Katie Mack...

Now back to the perennial sujet du jour: the subject of the day has to be coronavirus. It's been quite interesting week because of the vaccine aspect of this grabbing headlines all around the world. The hopefully temporary cessation of trials for the AstraZeneca/Oxford University vaccine, regarded as one of the leading candidates to vaccinate against coronavirus; this trial was temporarily suspended this week after one subject developed an adverse reaction. To explain a bit more: Clare Bryant, immunologist at the University of Cambridge. Clare, how often do these sorts of adverse reactions happen in clinical trials? Is it normal practice to just suspend a clinical trial like this pending investigation?

Clare - Hi Chris. Yes it is. The Oxford vaccine is the Phase 3 stage, so it's going into tens of thousands of people. And we know that vaccines can produce side effects: for example, the flu vaccine that we have every year can have side effects. But what's central here is the risk-benefits, so if you're going to have an adverse event, it needs to be a very rare one. Now we don't actually know if the incident that's happened is actually to do with the vaccine itself - it may not be. It may be that a patient who's received the vaccine has an unrelated problem that's occurred during this trial, but you have to then stop or pause the trial at that point to investigate whether or not the incident that has occurred is due to the vaccine or is completely unrelated. And that is obviously important; if it's unrelated, then that means the trial can carry on and progress; but if it's related to the trial then you need to take a look, a serious look, to understand what's happening, because clearly if you're aiming to vaccinate the planet - which we are, that's many millions, billions of people - then you obviously can't afford to have an adverse event that's occurring commonly, because then the risk-benefit of having the vaccine versus the side effects becomes lost. But on the positive side, there are currently, when I last looked, 32 clinical trials of vaccines currently ongoing. We know the success rate for a good vaccine is approximately one in 10, so we should potentially have three usable vaccines against COVID - if vaccination is going to work.

Chris - Katie, what's the mood, apropos vaccination, like in the US? Because obviously, Donald Trump has been making some suggestions that it's going to be pretty soon that America is going to have access to a vaccine. And then a whole bunch of pharmaceutical companies have all signed up, probably in response to this, saying, "well, we're not going to have any vaccine until we're all completely comfortable that it's safe".

Katie - It's a very interesting situation because there is a fairly large anti-vaccine problem in the US. Just for ordinary vaccines for things that where we know the vaccine is safe. There are situations where there's a lot of hesitancy and Donald Trump has, at some points sort of fueled that fire. And now he has this programme to try to very quickly put out a vaccine. And there's a lot of concern that he wants to really hurry it through in order for it to be a factor in the election. There's a lot of nervousness around the vaccine because there's not a lot of trust in the way the federal government is doing this. And then also in other ways, not a lot of trust in vaccines, in general, in certain communities. And so I think a lot of us are just very nervous about how this, how this is all playing out.

I did have a question about this vaccine situation. There is some concern about reinfection or whether or not a vaccine is going to be fully effective. I know that there are a lot of vaccines that we have out there, like flu vaccine, where there's some protection, but it's not perfect. Not everybody who gets the vaccine is actually protected, but it's enough to make a pretty big dent in the amount of transmission. And I'm wondering, are we optimistic that if a vaccine does work as expected, that it will give most people immunity? Enough that we can go about our lives? Or are we going to be wearing masks and doing distancing long after a vaccine is available to everyone?

克莱尔——最糟糕的情况显然是我们don't have a vaccine at all, but there are different grades of potential protection. So we could have a vaccine that stops you, the patient, getting the disease, but it doesn't stop you carrying the virus and shedding the virus. So if that was the case, then we probably would still have to wear masks because not everybody can be vaccinated. So people, for example, who are receiving immunosuppressive drugs for maybe cancer or for horrible immune diseases, they're not going to be able to generate a response against a vaccine. So what we would ideally aim for is a vaccine that would mean that you don't carry it, as well as you being protected against the effects of the infection and disease. And we just don't know at the moment where we are. And this is one of the concerns. So for example, somebody from Hong Kong, who had the infection and then was reinfected, that person had no symptoms, but they could still isolate virus from him. So potentially that person could still shed virus into the population. So this speaks to the concept of herd immunity - how many people do you need to be protected in order to stop the very susceptible groups of people actually getting infected. And these are all the unknowns.

克里斯-克莱尔,这个问题再感染,this obviously has rung some alarm bells, because people are saying, "well, if catching the virus sufficiently badly to put you in hospital doesn't then result in long term immunity and you can catch it again three months later, (which is what happened in a couple of cases that have now been written up), is this not a danger sign that a vaccine has got so much heavy lifting to do to make you long term immune that actually a reasonable proportion of people might not respond to it, which may be another fly in the ointment?"

Clare - Yeah, absolutely Chris. And I think that is a concern. And I think one of the problems, particularly with this virus, is the individual variation in the response to disease. So for example, some people that had a severe infection, most of those people tend to be older. Older people don't generate as good an immune response as younger people. And that might be part of the reason. And are we therefore going to be able to generate a vaccine that will generate protective immunity in these people if they're not protected after having a primary infection? Very difficult to say at the moment, the knowledge isn't there.

Chris - I was thinking of you earlier, Richard, when I was reading the headlines -

Richard - It always scares me when people say that!

Chris - ...because isn't it interesting that Donald Trump has taken a space analogy. They've got Operation Warp Speed to come up with this vaccine that's going to rescue the US and hopefully the rest of the world. And Boris Johnson at the 10 Downing Street press conference used the word, my Moonshot for a very ambitious programme of testing, both of which are obviously aiming to control coronavirus. I wonder why they're using space names. Do you think that's kind of, because it's ambition, it's kind of everyone getting together, it's enthusiasm and they're trying to garner some of the positive support around space?

Richard - Well, possibly, but I think that I would say the main reason is because space, again and again, with mission centered space exploration, has proved effective teamwork. Has proved a huge diverse group of people working together - with the Apollo programme to put people on the moon, tens of thousands of people involved, all working together. We've seen it with the Mars missions. We see it again and again in space. So I think they want a bit of that.

Chris - What do you think the sort of sentiment on the street is, in terms of people's enthusiasm for a vaccine? We've made mention of vaccine hesitancy. Do you think that damage has been done to the vaccine drive now by the fact that they've come out and said, "we're going to stop this trial", albeit temporarily, or do you think that people will find that reassuring? That proper checks and balances are being done?

Richard - I hope they find it reassuring. I mean the anti-vaccine movement, which Katie mentioned, has been around since the middle of the 19th century, it just has a louder voice, I would say, now. I think we should all be reassured that there are 32 groups around the world working on a vaccine. All those groups of scientists are not going to release anything until it's proved effective. So I think we should be reassured and frankly, oh, I would love a vaccine. I would love an effective vaccine. I want to go and hug people again. And I'm not the sort of person that likes hugging people.

Chris (to Clare) - I've got some questions here. Richard has been in touch and he says, when COVID-19 was first prevalent, we got told to maintain social distancing, wash hands frequently, avoid touching faces. He's saying it must be several weeks since he last heard anyone dwell on that advice. Has the advice changed, or is it just that people have got hand washing fatigue in terms of their messaging? And they've moved on to something else now Clare?

Clare - No, the advice hasn't changed. And in fact, I think Grant Schapps was on the radio this morning saying exactly that, that we need to remember to maintain the hand washing, not touching your face and so forth. Nothing's changed.

Chris - Got this one from Steven. And he's asking about the question of viral load. What he's referring to is how much virus you're deluged in when you're exposed to someone who's got the infection. And he says, um, it's been said that in some instances where symptoms are bad, the sick person has probably received a high viral load. Presumably this could be lots of close contact with sick people or a lot of fluid from just one individual, very sick person. So if you reverse this logic, will the receipt of a very low viral load mean someone is less sick or does it not work like that?

Clare - That's an interesting question, isn't it? I mean, it's certainly something we've talked about and that has been talked about a lot, but the problem is with that is that you're assuming that everybody will respond the same to a dose of the virus. And we know that there are some people who are super susceptible and some people who are not. So it would be a little bit like Russian roulette saying, "do you want to try this or do you want to not try it?" Um, it's not really an experiment I particularly want to participate in. I'd rather wait for a vaccine. Thank you.

Katie - I've been reading a lot about aerosol transmission and the controversies around what we mean by aerosol what we mean by airborne and so on. It seems to be that there's a kind of consensus growing that indoor spaces are particularly dangerous because the virus can be sort of floating around in the air. What's your perspective on that?

Clare - Yeah. I'm inclined to agree. I mean, it's a confusing space and, you know, we've thought about it a lot, particularly in drawing up of course, risk assessments for work. It's reasonably clear that outside spaces are safer than inside spaces because of airflow and much better ventilation. Obviously when you're in an inside space, particularly depending upon your building, a lot of buildings now require air recirculation, and you can anticipate as you recirculate air, if there's no direct connection with the outside world, then you're getting an accumulation of viral particles in a space where an infected person might be. So I think that's about the only thing I feel reasonably comfortable with, being outside is safer than being inside. This data will emerge over time. As we learn more about the virus of course, we learn more and more about the problems that are there.