Right. Could you start by saying your name and your current title? It's Matthew Snape,
and I'm vice president at the Madonna and Vice President for Paediatric Maternal Vaccine Clinical Development at Madonna Biotech UK.
And you also still have an association with the Oxford.
And I'm a visiting professor for the University of Oxford Department of Paediatrics.
Okay, fine. And I'm going back to the very beginning.
How did you first get interested in medicine and what have been your main kind of career staging posts on the way here?
Fair enough. I've been interested in medicine since as long as I can remember.
I actually have always wanted to be a doctor. And it's I even have a magazine for my primary school asking, what are you going to be when you grow up?
And I say, Doctor, it's just always been I've always been interested in natural sciences and I've always wanted to, at one level or other, be useful.
And so that kind of work was a fairly and was doing well enough at school that it seemed a fairly good fit.
So that was from so I started medical school at 17 and that was in Melbourne.
That's right. So I went from Melbourne and loved my rotation through paediatrics, so I thought that might work for me.
And so then two years in my second year after qualifying started in paediatrics
went to be actually training at the Royal Children's Hospital in Melbourne
from three years training at Royal Children's then actually had always thought
that I would like to come over and do some time overseas and train overseas.
And so and so came to London and worked at St Mary's in intensive care where I was dealing with children in the intensive care unit who
were getting very sick and poorly from and dying from meningitis and sepsis in particular at that time due to meningococcal disease.
So that's there meningitis bacteria. There was a lot of focus at that time about developing vaccines to prevent that.
And particular a vaccine had been introduced called Mincy, that was having a dramatic effect in reducing the number of cases of Mincy disease.
It was still seeing a lot of men be. And so, as I saw as well, and different versions of the same bacteria.
So which is much harder to make a vaccine for. And so that was kind of piqued my interest as to how would you do that?
How did you get involved in that kind of work?
And then I heard that there was this guy, Andy Pollard, who was doing a lot of interesting work up the Oxford Vaccine Group.
He'd recently been through his St Mary's intensive care unit as well.
So I went and had a chat with him and there was a job available and so started that 2003 and been there since until very recently.
Yeah. And so your you took on them and the problem did you is that initially there was some other versions actually.
I mean I CWI which covered some other types and then in 2006 was Menb.
And so that vaccine was eventually that's working with.
And one of the things about the Oxford Vaccine Group, it's never been too worried about working with industry and collaboration.
And so this is what was happening at that time that a vaccine manufacturer initially, Kyra,
and then Novartis were developing a vaccine and were looking for trial units with who are able to do paediatric studies,
run vaccine studies in children. And so that's that's your area.
But you're not working in the lab. I'm not working on paediatrician now.
Yeah, that's right. So very much helping to run the clinical trials.
At that point I was a research fellow, helping to run the clinical trials to actually enrol children,
to take blood, received this vaccine to see if they met an immune response.
And so we were quite involved in the early studies of those very early stages of what eventually became a vaccine called Bexsero,
which is routinely administered to all infants in the UK.
Now what are the special issues that arise in trying to trial vaccines in children?
Obviously we have to pass a very high safety threshold before you can go in and see almost
always given to adults first and then stage down through different age groups now.
So it went very quickly to infants because that's where the disease was happening.
These were the children. It were suffering. So you could have gone through another few years of checking it in teenagers or older children.
Those studies did happen, but it was really important very early on to see does this work in infants?
Because this that's going to be the core when it's going to be given so that otherwise it would have cost several years of development.
And in that meantime, more children die. And this is the point.
You know, you can be very, very safe, take 20 years to develop a vaccine.
And in the meantime, children are dying. So that's what you've got to get that balance right.
So it went relatively quickly into children and you have to obviously convince parents that they would like to enrol their child in a study.
Um, you often find as parents who've had experience within the family of someone who suffered from that disease,
a cousin, a nephew, one of the other children, even so,
they might put their child forward to have some blood test and receive a vaccine that we don't know whether or not it will work or be randomised to a.
Placebo, a saline or some other controlled vaccine.
So there's challenges there of getting it. The regulators like the MHRA and the Ethics Committee happy that you're doing the
study well and to a safe standard and then enrolling parents in enrolling children.
And even the logistics of getting blood from a small baby, you need very highly trained staff who used to doing this.
Just to give an idea of the logistics, in order to actually make this happen, we would for our paediatric studies in young children studies.
We have a mobile team of doctors and nurses that go out to the homes all through the Thames Valley.
So based in Oxford, but would go within basically a one hour driving radius.
So all through Berkshire,
Buckinghamshire and Oxfordshire with teams of nurses and doctors that go out to the homes of these families and can take the blood,
get the vaccines at homes and that kind of personal approach and actually us going to them actually helps us enrol and keeps children in the study.
And we actually deliver those studies, I think, to a high standard. Mm hmm.
So what year was it that it became adopted as a standard that was licensed and approved in 2013?
And I think it was actually introduced. It was introduced in 2015.
There was a several year delay of negotiating the terms and contracting to actually get it introduced.
But it has been introduced in 2015 and we've seen a significant reduction in members since then on that.
Well, it was going down anyway, so that's one of the actual strides in the development.
You know, the need for a main vaccine was identified in the early 2000s.
And you actually, you know, there's been for decades really attempts to go on. But there was a big surge in cases around that time.
And then for reasons that aren't entirely clear,
it's actually been going down by itself that might be related to even things like reduction of smoking in pubs,
because you're less likely to carry that dangerous bacteria in your throat if you're not smoking or if you're going to expose to cigarette smoke.
Very clearly across many countries, there's been a decline as the vaccine was being developed.
So which is great. But yeah, it was actually a touch and go thing whether the vaccine was going to be introduced.
But it has saved hundreds of lives in the UK over it since it's been introduced and of say again
actually I'll rephrase that has saved hundreds of cases of invasive meningococcal disease,
meningitis or sepsis in the UK and is used around the world as well.
So it's having a broader impact quite globally. And you've worked on some of the vaccines as well.
Yeah. So that's been, uh, so some of the key landmarks was the, the meningococcal vaccines.
We were involved in the swine flu studies when swine flu came through in 2009.
And so testing again and that really each that we were learning how to do this.
So swine flu came along. We need to enrol a thousand children in six weeks to receive two versions of the swine flu vaccine.
We quickly realised that was going to be a collaboration with Public Health England.
We quickly realised we couldn't do that ourselves with the Oxford Vaccine Group,
that we could do it if we did it as a network working with Southampton and Bristol and St George's, so forth,
that together each to play their part and you know, amazing,
unprecedented that you could enrol a thousand children over six, over six weeks for what was an investigational vaccine.
And again, the logistics of making sure that work, you know,
actually just conducted in paediatric outpatient clinics over weekends, getting whole teams in,
getting almost a conveyor belt approach to the children going from station to station so that we could make it as efficient as possible.
We learnt it, we there were some, there were some teething problems no doubt,
but we all learnt a lot in that study about how to coordinate as a group and in fact
started a tradition of every Monday evening having a call between those sites to.
Check check in with each other, see how things were going for that particular study.
But that actually has continued on since 2009 now. Fortnightly Usually things that we will just check on,
see what's going on with our different studies and how we can support each other and how it's working.
That really developed network almost overnight. Yeah, that's really useful.
Yeah. And how old were those children? They were from six months to 12 years of age.
Right. Yeah. To see how vulnerable our children in that age group to flu.
Well, that was the big unknown.
If you take mine back to 2009, you know, swine flu was going to be the big pandemic and never quite fortunately took off to that extent.
So, um, but we do know that during the pandemic, around 70 children died from influenza.
So it was not trivial. Many hundreds of thousands were immunised.
So that number may have been higher if they weren't immunised. But fortunately, swine flu never quite took off, as I say as that as was feared,
the age groups most vulnerable to flu under two years of age and then the elderly traditionally.
And one of the reasons we were very interested in immunising children is that they're very good at spreading it to the elderly.
And so one way of trying to control the disease, and you will have had it once talked a lot about herd immunity and so on,
but especially for flu, it's a quite established model that to reduce influenza circulation in the community, immunised children.
Mm hmm. And if that pandemic had kicked off, then one of the early steps would have been to shut down schools for the same reason that.
Even and probably much more so than COVID influenza spreads among school age children.
Yeah. So you've mentioned COVID. Let's get to it.
Finally. Yeah. One more stop along the way.
Swine flu. And then we were involved in the Ebola vaccine studies.
So we did first in human Ebola studies for a vaccine that is now approved by the European Medicines Agency for use in ring vaccination.
So that was working with Janssen. So that was another key milestone, all of these kind of letters.
And again, that was a very rapid, you know, we had to go from from nowhere to starting enrolling within a month or two.
And again, we learned how to do things quickly.
And where did you carry out that study that was done in UK volunteers, healthy volunteers, because it was well, it was first in human.
They wanted people with no prior Ebola exposure.
And again, just to look at safety and immune responses in people who were seeing the vaccine for the first time and great response then we well,
very quickly, you know. So, yes, I mean, you were obviously in a very good location to be alert to what was going on in China.
But can you remember when you first thought this is sounding pretty bad and it might be something we need to get involved with?
Yes. So there was obviously the message coming from China and we were looking at that.
I think I mean, I've already mentioned that I've been involved with two previous outbreaks which didn't quite take off,
you know, about was awful in West Africa. And it was people were worried at one point about a global pandemic.
That didn't happen.
People worried about swine flu, that there was there was there was a lot of people sick with it, but it never took off to this extent.
So it was always, well, which one is this going to be? And I was joking. It's every five years because it has been every five years.
But the one I've left out is bird flu 2005 bird flu 2009 Swine Flu 2014.
Ebola 2019. Over it was I'm Kenya. So okay.
Here we go again. What's this one going to be like and is this going to fizzle out?
Probably we're going to be involved one way or another because we have been for all the previous ones.
And what what will that involvement look like? I was I was brought in when it became apparent that we had I first became involved in the discussions
when it became apparent that the Sera and test were developing their vaccine and I think fill you in on
became apparent that you know we'd had that experience of doing vaccine studies quickly and at scale and
whereas usually the model would be whoever is developing the vaccine will do their own clinical trials,
think very sensibly people realise that it makes sense for the Oxford Vaccine Group to get involved and to deliver that.
We had the infrastructure, we had the staff, the project managers that the systems and we're an accredited clinical trials unit.
So that's when I started to be hearing about it probably in February or so as to where we were going to that we were going to there is a vaccine,
we are going to be involved in delivering it and we need to think about how we're going to do that.
Yeah, well I've talked to and these I we've gone over the development of the trials from from his perspective,
what was your particular role during those that support?
A little bit of training, actually. I remember when we can run just writing out what are the questions that people are going to ask about,
you know, volunteers and preparing a standardised set of answers, frequently asked questions.
It sounds trivial, but it's so important to get the message right.
There's so many different angles of that that were coming along so quickly that we had to think about,
Well, if somebody asks about genetic mutations, if somebody asks us about the animal studies,
you know, what is a standard response that we've got hundreds of nurses and doctors working on this across multiple sites,
which it's not an official document. It's one that's prepared mostly.
We used to prepare internally that people could read through and be prepared, but then can be used could be used by the other sites as well.
So that was one thing that I prepared and another was, as I say, somewhat notoriously involved in preparing a video consent.
So rather than having to have 20 minutes or so,
1 to 1 face to face of a doctor or nurse explaining the study that all the volunteers watched the video beforehand
so that they would get most information and could just ask any questions before they had the consent form.
I did not enjoy that process.
I was kind of put up for it and the auto queue was a one speed auto queue that could not speed up or slow down and it was either
too fast or too slow and it took about 6 hours of takes to prepare a 20 minute video with the evening getting colder and colder,
not being able to turn the heating on. And I was really just shivering by the end of the train so that we couldn't do that.
It was awful because of the noise, the background noise. You couldn't hear the noise.
Yeah. The only hater we had. Yeah, yeah. And the heat is we had been noisy so.
Yeah. And the, and from at least one of those videos was done with a pretty bad lockdown haircut.
So Seth, I can hardly. Myself to watch them that they got the information across.
You know, it was an efficient way of doing.
And that was the you know, a lot of this stuff was putting ego aside, saying, well, it needs to be done so I can do it.
And the and said that was done. So it was one of the things that was done alongside that.
I was running a study looking at how commonly children were getting infections,
taking blood tests from children, but not to 18 years of age, actually even slightly to young adults.
And so that was called what's the story serum testing.
So it's a zero epidemiology study. So it was trying to keep that going and also having to wind down a lot of other studies.
It was very traumatic. There was lots of reasons that, you know, there was a lot of terrible things going on.
And fortunately, you know.
It wasn't affected personally by the by relatives or friends becoming terribly sick or or dying, at least not in the early stages.
But it was also still quite traumatic,
just the impact that you've been working on various studies for years and now having to shut everything down in particular.
One study I was working on was looking at meningococcal carriage in the throats of teenagers.
We were delivering at three schools. We enrolled 24,000 teenagers to this study and then had to stop it because the school shut down.
And so I was doing a lot of tidying up of trying to just get those things sorted and working out.
Can we do the study and realising we couldn't, all those kinds of things? So 2020 was a very strange year for me.
So I was involved to some extent with the CO, but perhaps not. Those initial studies had a role, perhaps not a central role, as you know,
in retrospect I would have liked to have had or if you doing it all differently,
perhaps I would have just quickly moved away from those other studies and realised they were done and just got myself embedded with the core team.
But I was able to do a few useful things and I think that was that was helpful.
I don't I mean, I would did want to talk to you more about the serology study.
So I mean, you must have immediately of thought from what you know about flu, can we pause?
Yeah. So we could talk about the serology, the serology study. So this was this study predated the pandemic.
This is when we were. Tasked in collaboration with Public Health England of conducting a study that was going to obtain
a sample of blood from a representative selection of children and teenagers across the UK.
And this is to try to see if there are any gaps in the immunisation schedule.
This is this was to try and see if there were any gaps being left by the UK immunisation schedule in protection against vaccine preventable diseases.
For example, within a few outbreaks of diphtheria in the north east.
So they're trying to see what were their particular ages, whether antibody levels against diphtheria or tetanus or Mincy were particularly low.
So that's what we set up. And so it was planned plan to enrol 2000 or so teenagers.
It was quite novel, hadn't been done before and we were really looking at learning how to do it.
And I do remember telling public health in saying to public health England, you know, this would be great.
And of course, I need your expertise on how to do a zero, on how to do a zero epidemiology study.
We can recruit the children, but we need the academic background. And then everything changed, obviously became we could see that it would be useful.
And this was one way many people around the world were doing zero epidemiology studies.
We had an ethics approval. We could get this going.
And so I felt that we could really get going with this and actually got permission to continue this study.
You had to go through a selection process, the Urgent Health Priority Select Committee,
to see if your research was important enough to continue during the pandemic and whether it was relevant to COVID or not.
Obviously, many studies were shut down. So we got through that committee.
We got some extra funding to expand the study slightly, and so went from there.
So then we were looking for COVID antibodies. We exactly.
So the idea is that we would then, you know, we'd already taken some started collecting samples, very few at that point.
But from now on and we'll be testing those in any future samples for antibodies into COVID.
So tracking infection rates in children and teenagers.
So it's a study that we've published the data and I think the useful data, we never quite got things we about as quickly as we would have liked.
It's fair to say, and particularly the results from the testing,
the blood tests never came back to be quite quickly enough to be relevant to UK policy, which was frustrating.
It was a dphil student, Helen Ratcliffe, who worked on that, has done a great job.
And so, as I say, it's published that we hoped that we'd be able to get things turned around, you know, within weeks was what would be useful,
but with delays in terms of needing support from groups such as NHS Digital
to be able to do the mail outs to recruit representative groups of children
rather than just getting whoever wanted to come forward and then apply some delay in working out which assets we're going to use to test this.
That's Public Health England very much wanting to say we will use one assay and go from there.
And it all was a slower and harder than we would have liked to think,
but we did and role and we continue to and rolling through the pandemic so you can really see the different patterns
of infection that were occurring initially in London then then in higher rates in London and then in the north west.
You can absolutely track the outbreak of the increase in infections in secondary school students in September, October 2020.
You can absolutely see that this was happening and was real and antibody levels going up
that wasn't affecting younger children at that point and then they came along after that.
So you can see the patterns going through. So I think it's quite an interesting kind of record of what was going on.
We hope that we'll be able to inform decisions like school opening and reopening, but I don't think we really got to that point.
What we can say is that we know, for example, 30% of teenagers had antibodies,
had had an infection for teenage immunisation was rolled out and that's quite relevant to thinking about cost benefit,
you know, of what was going on and exactly what you're achieving by giving vaccine to that age group.
And actually did they need two doses, always met one dose if you knew which 30% they were.
One dose would have been fine, but obviously we didn't. So you have to go from there.
So it was interesting, important. And did you compare the antibody levels with how many children had actually been sick?
Yes, we're able to see that only half children being sick.
And so, you know, half half of those with antibodies had had subclinical infection, no symptoms.
And very few symptoms were predictive of having had an infection in children,
young in teenagers, you could say perhaps loss of taste and loss of smell.
Some of those classic old adult symptoms in younger children.
You couldn't tell from any other respiratory infection, see, all the time.
Yeah, that's right. And it was those that loss of taste, loss of smell, you know, obviously a two year old.
You can't tell if they've lost their smell.
But even if the primary school aged children, you couldn't they were very poorly predictive of having or not having had COVID.
So that's all interesting and important for all of this.
Everybody and rightly was trying to do stuff that was going to make a difference tomorrow.
And I don't think we achieved that is quite as well as we would as we possibly were.
I think the the starting of it, the bones of it, how it was structured before the pandemic was to do it really were in.
Well and get a really precise sampling across all demographics and, you know, to get a very balanced.
And so that was a quite intentionally a bit of a kind of slow, deliberate process that didn't really adapt itself so well to it.
Would we could have possibly just gone and said, let's just get whoever wants to take part.
Yes, it will be over. There will be an overrepresentation of white middle class people,
but if we get enough people, then we can account for that in a positive way in retrospect,
and we halfway through adapted it to include repeat samples, which is another approach to take repeat, repeat, cross-sectional sampling.
So we could send children the same children repeatedly so you can track who's getting infections.
And we did that. And actually that was quite good because one of the things we've got uniquely and we're just looking to publish this is to show
that having baseline immunity against the seasonal coronaviruses that you hear about does not protect children against SARS-CoV-2.
And this we've shown this probably, I think, more convincingly than anyone else that one of the theories as to why children don't get sick with
COVID was they had immunity from seasonal coronaviruses that they're being exposed to all the time.
But that did not seem to protect you against infection. And that's been one of the contentious arguments.
So yeah, and so this is a nice paper that's coming out. You know, this is all taken longer than we would have liked.
This was not the top protein that was in let's be honest. It was a feature within the vaccine group.
There's only so many people to do that. Most of them are working on a project that's going to save the world.
There were one or two people that were working on this side project, so perhaps we were able to kind of brush it through.
So in some ways it was quite a frustrating experience while being helpful and it contributing to the actual main story.
Some of my particular things that I was trying to get going weren't able to get going as well as we would have and others have shared that experience.
And it's not to be expected. It's to be expected and completely understandable.
But it is also understandable if are a little bit frustrated that actually, you know,
there is just no one and there are very few people left to help deliver this what I have been set up to do.
And so that kind of for me the, the, the project that I feel made the biggest contribution directly would be the,
the, the Concorde studies, which started in with a phone call around September or so and com means.
Yeah. So that's the combination. Oh what does it mean they have to these acronyms we came up with but compare comparing COVID vaccine schedules.
Yeah. Is something what it is we had also it's original it was called combo but we got some feedback that that sounded like a jazz band.
So we call from Jonathan Van-tam in September or thereabouts saying, Matthew Chief Medical Officer Yeah.
Deputy Chief Medical Officer I'll take a step back.
The reason I was doing the story study,
the epidemiology study was I was leading a consortium called Nice Sick National Immunisation Schedule Evaluation Consortium,
and that was one of my main jobs. And the job of that group was to do vaccine research of relevant to UK immunisation policy.
So that's where that epidemiology started came along and we're doing one or two other things related to that.
So clinical trials or other research that was going to inform UK vaccine policy and
he so it's mostly for vaccines that are already approved and then you work out,
you do tests on them. So in September or so, the call from Jonathan Van-tam Deputy Chief Medical Officer It was Matthew.
There are going to be vaccines available in December. This is what it's looking like.
And one of the big questions we have is whether you they whether you have to stick
to the same vaccine or whether whether you're locked into the same vaccine.
Is your second dose as your first dose? Yeah. So the assumption is already made that you need two doses that we knew.
That's right. And that was part of that conversation. We knew then that Pfizer was a two dose schedule.
We knew that the Oxford AstraZeneca vaccine was initially thought of as a one dose schedule, which was interesting.
And then the second dose was added in later on. But yes, both of we're looking at two dose schedules.
And if you receive vaccine for your first dose, you still locked into getting vaccine next year, second dose, or could you receive vaccine?
Why? If there was a supply problem with vaccine or a safety signal with vaccine that suddenly meant everyone's got to use vaccine.
Why? They wanted programmatically to understand that logistically that was an issue.
But also scientifically, everybody was immediately saying, well, that's a really interesting question,
actually, because there could be advantages to mixing and matching these vaccines, whatever we call it.
Everyone immediately called it the mix and match study. So that was the idea.
We felt that was too informal or colloquial, a title or footnote a title.
And then the Americans, when the study called Mix and Match Study say so with two different studies, Atlantic doing different things.
We I mean, we're very proud of that study because it was it was a it was a randomised controlled trial
enrolling people at the first dose and and this is after the vaccines have been like.
Yeah that's right. So.
We planned it through the last quarter of 2020 with a view to launching as soon as possible in 2021 after the vaccines were available.
We remember that vaccines started immunising just around Christmas in 2020,
and we asked Pfizer if they would provide us the vaccine ahead of time, and they said no.
So we had to wait till it was available. They said we shouldn't be doing this study because it will create confusion.
And what if there's a safety signal in your study after a mixed schedule, then potentially both vaccines will be jeopardised by that.
I'll be frank, they didn't that I think they said if you if you are concerned about there not being enough of our vaccine, buy more of our vaccine.
So they didn't want to do that.
Ironically, once we were doing the study and had the results and they could see that it was going to be incredibly useful to get these data,
they were asking us if we could ship them some blood samples so they could do their own testing quicker than us.
Please. Thanks very much. And so we said no, the.
So, no, they made a strategic decision not to provide their vaccines ahead of their available availability through the NHS.
So in the end, yes,
we had vaccines sourced through the NHS and the NHS did this really well in the Unite trial and the Vaccine Taskforce know they set up a
specific group that we met with weekly to help us make sure the study was moving ahead and was going well and to see where the blocks were,
what we could do about it. And they were checking on us and we'll also providing support.
So ordinary members of the public like me, just got two of the same as a default?
That's right. Yeah, but the people in the study might or might not get tested.
And this was a randomised controlled blinded, single blinded study.
So you would we were looking for people 50 years and above.
We'll give them the briefing. J. Jonathan Van-tam that this was not to enrol young, fit, white people.
This had to be more diverse than that. And so we had to stay ahead of the roll out the rollout of the vaccines.
So we had to we knew that strategically the group to enrol were those that were just about due to get this vaccine but hadn't got it yet.
So over 70 year olds were really getting their vaccine. So we went to 50 plus and we recruited 50 to 70 year olds.
We had such interest in the study. We could have enrolled it ten times over.
We enrolled about 850 people. We could have enrolled that ten times over, which was good,
because that meant we could actually actively prioritise recruitment of people with co-morbidities, you know,
underlying health problems, lung, cardiovascular, whatever else,
those that were most likely to get sick, and also people from non-white ethnic minority groups.
So we the enrolment rate for that was around 23%, which is very high for these types of studies.
And I think that was that was great. So in that initial study we were looking at the Oxford-astrazeneca vaccine or Pfizer and
giving the standard schedules and comparing standard schedule with a mixed schedule.
So we're also looking at intervals at the same time, is that right?
Well, that's how it evolved. That's right.
When people say the initial design was that everybody got it at four weeks and then when the decision was made,
very good decision that actually they're going to prioritise the first dose.
And so people will wait longer for their second dose and the schedule wait pushed out to 12 weeks.
Then we said, okay, well we already had a design that had four weeks in there and that was fairly well advanced.
So we didn't want to just scrap them, thought, well, this is a good opportunity, let's look at randomised study comparing four weeks versus 12 weeks.
So in the end the eight arms,
it was some call it the octopus study that you had two doses of AstraZeneca or two doses of Pfizer or AstraZeneca, Pfizer or Pfizer.
AstraZeneca. And then that could be given it either four or eight weeks.
And so it I mean, methodologically,
it is the kind of cleanest study of its type because they were properly randomised and and so you could really get true comparisons.
It wasn't to a kind of convenient sample or observational or let's take some people who got a dose and let's give them something else.
But everybody was getting all the vaccine. They needed that.
Exactly. They'll get in two doses and we didn't know how well it was going to work.
We just did not know whether there was a full expectation that it would be okay.
There was a reasonable expectation. There might be advantages to mixing and matching.
And the schedule that people were putting their money on was going to have.
The best response was probably with the Oxford-astrazeneca vaccine and boosting with Pfizer.
That was thought to be viral vector followed the RNA.
That's the two technologies that was thought to be important for thinking that would be that viral vector would prime really well and
generate a T cell response at the first dose and that they could boost with the irony that was generating a protein in a different manner.
And that could really well, what we saw in the end and the actual question,
specific question we were doing was it called a non-inferiority study if you've had vaccine at your first dose?
Are you any worse off if you get faxing the second place, or is it as good as.
If it had Pfizer, sorry, if it had the Oxford-astrazeneca vaccine and you receive Pfizer for the second dose,
not only were you as good as you are actually better off, you know,
the antibodies were higher than if you got two doses of the Oxford-astrazeneca vaccine.
If you got a first dose of the Pfizer vaccine and the second dose was the Oxford-astrazeneca vaccine actually around,
bodies were lower and your T cell responses were lower than if you got two doses of Pfizer.
People are a bit surprised by that. They were the two specific questions we were asking.
But obviously, that also allows a direct head to head comparison of the Oxford-astrazeneca vaccine versus Pfizer, two doses.
And what we saw, in fact, was that the Pfizer vaccine generated antibodies that were ten times higher than the Oxford-astrazeneca vaccine.
And that was that was an interesting moment when that kind of realised, especially being within the Oxford Vaccine Group,
the atmosphere in the group when that result came in,
the atmosphere was that we know that the Oxford, this is a message that has to be handled carefully.
And I absolutely got this. This wasn't all being kind of silenced or anything else like this I could immediately see.
This could be in the wrong hands, really unhelpful.
We know that the Oxford-astrazeneca vaccine prevents severe disease, prevents infection.
We know the efficacy. We know it's very good at preventing severe disease and hospitalisation.
And we know that there's a lot of this vaccine available in this country.
And the worst thing that people could be doing is starting to kind of shop around for this chosen vaccine.
If that happens, then more people will die because there wasn't enough to go around that oxford-astrazeneca is very good protection against disease.
So the key message was had to still be get the vaccine that's being offered.
And so what we the messaging we put out was an accurate one, saying, well, the Oxford-astrazeneca vaccine sets a baseline.
We know that it's effective and all of the combinations we looked at were higher than that.
All of the other combinations were higher than that.
But there's no doubt it gave pause for thought to saying, well, you know, ten times higher, that's a lot higher.
And and there was a surprise translate into ten times as many people saved.
I mean, it's not as crude. It's exactly that is all you need is enough.
And that was the message is saying is more better or is enough enough. Was one of the cases and was saying enough is enough.
You know, this is good enough and this will provide protection.
This was still in the kind of before Beta Delta, Omega and especially Omicron had come on.
There was no magic to the different combinations.
So it wasn't as if having this, you know, having the viral vector first followed by RNA was just a better thing overall.
Actually, it was just getting an RNA vaccine gave you a higher antibody responses,
though some surprised it also gave you higher T cell responses because there'd been a big
play that the viral vectored vaccines were very good at generating cell mediated immunity.
And really one of the key things we were able to do in is really it was quite an achievement in a study of this size
was working with a lab called Oxford Immune Attack that were able to process T cell samples at scale to a kind
of because they're harder the harder than antibody testing antibody testing you take the bloody spin at turn you
put in a fridge tested T cell samples need to be processed the next day you need to take out the white cells.
There's a whole it's it's a lot more complicated.
We got all of those samples done and and really robust results from them in a randomised controlled trial in hundreds of people.
And they showed very clearly that actually the Pfizer vaccine generated that T cells that were as high,
if not higher than the Oxford-astrazeneca vaccine best actually for this one.
The combinations did start to throw up some interesting things that the best response was the T cells was oxford-astrazeneca followed by RNA there.
The mix and match did seem to help. In particular, they got a better response overall.
So that was that was interesting.
Yeah, I think it made some awkward conversations with Oxford-astrazeneca and, and others because we were very open with all the manufacturers.
We would present the data when we had it and we present it to the vaccines.
Minister very early on, one of the quite a slight delay was that we got two ways of testing the antibodies.
One is to do a binding antibody and one is to look at neutralising antibodies.
Bind to the virus or do you and do antibodies kill the virus?
That latter test takes longer and we needed we.
Before we put that in the results, we wanted to make sure that what we're seeing in binding was also reflected in the neutralising.
And so that actually caused a delay of a few weeks. In the meantime, we were scooped by a study group in Spain.
So there is always a frustration. It's always something you wish you could have done quicker or something else like that if we don't.
Yes. So a lot of these things that were trying to standardise so those tests were being done by a company in Canada called Next Ellis.
Then there was some, you know, they were doing a lot of testing and so there was some delay in getting those results.
We could have done it more quickly locally, that it wouldn't have been standard. There's always things you could do.
So that was that study. We also showed that actually giving the vaccines in mixed combinations was caused more reactions.
So that was interesting. That was the first paper that came out. What kinds of reactions look?
Temporary reactions. So fever and sore arms and feeling poorly in the few days after the vaccine, but not serious.
Nothing. No safety signals. No safety signals you don't really expect to see in a strange way, you know,
safety signals in a study of 800 people, you know, what you can tell is what the standard reactions are like.
You can't pick up a one in 10,000 reaction, but we would we will be very surprised to have to pick up anything.
So why we were doing all of that.
Then there was the safety the safety signal from the routine rollout about the Oxford-astrazeneca vaccine, about the blood clots and the changes.
So suddenly what the study had been set up to do became immediately relevant and that people all around
the world were getting the Pfizer or RNA vaccine at a second dose if they'd had it for the first dose.
So that was gratifying to see.
Will probably again a few weeks behind the policy change kind of people were getting that schedule by the time we were able to publish the results,
but at least will provide reassurance that yes, this does generate a good immune response.
We did show it was more react genic when it was given it four weeks interval.
Eventually we have to show that that didn't react to it cause more temporary side effects eventually up.
That didn't apply as much when you gave that at 12 weeks, which was what was happening.
And so yeah, there were a few weeks there where we were on the phone every day to all the different vaccine advisory boards around the world,
you know, Portugal, Spain, Germany, Scandinavia, Canada, US presenting these data, that was very exciting,
you know, saying this is what it looks like if you make vaccines.
So that that was very exciting and gratifying and obviously good publications, good public health impact.
That's the main thing, the fascinating science.
And then we were able to redo that or kind of replicate that study, if you like,
with additional vaccines thrown in and Novavax and Moderna to again look at priming with
AstraZeneca or Pfizer vaccines and then boosting with the same again or Moderna or Novavax.
So again, that provided some additional insights with Novavax in particular being quite interesting.
And, and in that mixed schedule in that age group, a little bit disappointing.
And weirdly we've shown that if you that for that particular schedule.
Pfizer, the particular schedule, Pfizer, followed by Novavax.
You get a very different response in 50 to 70 year olds compared to teenagers, which is study with them subsequently.
So that's that's a whole other story we need to look into.
So it's it's an interesting and quite complicated story overall, and yet it's still going on.
Yes. So combo of one and two. It stopped the Concord three, which is the one that's looking in teenagers.
So then again, August 20, 21, just when we thought we were able to kind of take a little bit of a break,
I get another phone call from Jonathan Van-tam saying we need to work out how to immunise teenagers.
There is a signal of my car itis coming along for Pfizer and Moderna for the RNA vaccines.
That is inflammation of the heart or pericarditis, inflammation around the heart and in green and tequila, very rare.
But the those who are experienced most commonly where we're talking around one in 15,000, that kind of thing, young males.
And so is a worry that, well, mostly COVID is not severe in teenagers and children.
There is this rare side effect. If you give two doses, especially the second dose of the RNA vaccines, it's more that's when it's more common.
So could we be looking at are they giving a smaller dose at the second dose or another vaccine such as Novavax?
So three and those results have been presented just looking to be published at the moment.
And and we're now also of another version of that study.
Now, the stage of that study looking at the third dose and different options for the third dose and that still recruiting.
Do you want to go? Okay. So let's let's talk a bit about vaccinating children and teenagers.
It was very contentious.
It was something that was in the press a lot about whether or not it was necessary to vaccinate them at all with one group of people saying,
how would you not vaccinate children? It's it's a no brainer.
And another lot of people saying, why would you vaccinate them when they don't need it?
That's a very crude. No, no, no, no. Look, the stakes were much lower than immunising eight year old.
That's very clear. These were the people that were dying from an 80 year old were dying from it.
So the stakes were much lower than that. And it's interesting matter of how things look.
It's all everything is relative. So, sure, a 12 year old had a much lower risk of dying from COVID than an 80 year old.
But as it's gone through, and particularly with the new variants like Macron,
that actually the disease pattern has changed so that young children do get sick from COVID and
end up in hospital with about the same frequency that they would with other vaccines that you do.
It is easy to immunise against influenza. So it becomes a little bit of a strange one where, okay, so it's a,
it's a relative thing where it's a bit of a strange one where you're intuitively, well,
they don't get sick as much as 80 year old, but they do get sick with the same kind of frequency as you might with influenza or something like that.
So if there was limited supply of vaccine, clearly you need to do the elderly and actually boost the elderly more than I would say immunise children.
By the time it got to children, many had already had an infection. So there is benefit and change there.
But then we know in crime came along, you know,
we realised you needed booster doses and that and that young children particularly are getting sick more commonly.
The UK is not. God is hard on young childhood infection as some European countries and the America has.
I personally I don't think it's a big priority in terms of of immunising.
What we're going to do with these vaccines, what can do with health care resources. Now, that's my personal view.
I work for a company that makes now that makes vaccines that are being tested in children.
So, you know, that is my own personal view.
And there's another issue which we should just address, which is the ethical the ethics around immunising children,
because they are a cauldron of what's what, a crucible of infection in which they can spread to other people.
And I was going to get onto that because that was the argument initially, you know,
and we're so used to thinking about this from influenza and other things.
And you know,
I was reading an article for The Guardian saying fairly often that we should only be immunising children if they're shown to be spreaders.
And if the vaccines stop, that's going to stop the spread.
That was before it became apparent that with some of these new variants, they were being getting sick more commonly.
But by the time we got to that,
it was clear that by the time we get to Home-grown that actually the vaccines were providing reasonable protection against severe disease,
but pretty poor protection against infection. So that argument didn't hold up any more that we could immunise teenagers that will stop them getting
an infection and that will take their family and their grandparents only for a few weeks at most.
So we and probably people were saying that for too long.
You know, we've got to immunise children, got to immunise teenagers because that protects the herd.
It stops the spread of the virus and people. I think some of the public health messaging was a bit slow to adapt to that.
And in fact, most recently when you look at Booster, they're not saying that anymore actually.
But even in the public information that's handed out, they're really downplaying the benefit of herd immunity and stopping the spread.
So I think herd immunity, let's just pick up on that phrase because it was it was notoriously mentioned very early on.
Yes. By 11 figures and then hastily withdrawn.
But absolutely. With hindsight, would you now say that the the the phenomenon of herd herd immunity simply doesn't really apply in the case of COVID?
Sure. Two or three things within that. One is that herd immunity is often referred to in the context of immunisation that you generate.
You immunise 80, 85, 90% of the population you generate herd.
Measles is the classic example, which I doubt if you immunise enough people,
even those that don't have the infection will be protected or those that are immunocompromised will protect.
Fantastic. There's no debating. That is a real and important phenomenon.
Probably. It's actually for most vaccines, it's more important than the direct protection for COVID.
Yes, it's initially it was used in the context of infection that if enough people get infection and yeah,
this a lot of things were said at the beginning that when people didn't know very much, they now look.
Odd and wrong, but people are acting on the information they had at the time and people were saying,
yes, if we senior government people were saying and it was semi policy at one point,
if we can squash the sombrero, people remember that phrase have people with a steady rate of infection during summer and
by next winter enough people will have had infection that the NHS won't be overwhelmed.
So it was very much about protecting the NHS.
One of the other phrases. Steady rates of infection will mean that the NHS isn't overwhelmed.
Now that was not going to work. We know that now and that was going to lead.
If that policy had been and that was an argument to avoid excessive lockdown.
We know what happened. And we know that that didn't pan out that way.
And and that policy, if left unchecked, can lead to excess deaths.
In terms of herd immunity for vaccines? No, I don't think we have vaccines by themselves then.
By themselves, it is clear that, yes, they also don't protect reinfection.
And so you can't generate herd immunity if you're not protecting reinfection.
Are we going to eventually get to the point where people have had enough vaccines
and enough natural infections that they do get immunity and stop getting this virus?
We're not there yet, so I hope we will get there.
That's the expectation. And that will depend on what the virus is got in store for us in terms of mutations and evading immunity.
It's been very good at that so far. And we this is how viruses work.
We apply natural selection. If we're immune to this variant that will select that for a new variant that can escape.
That's what's been happening. So no, we have not really achieved herd immunity with this.
Perhaps it could be argued there wasn't. Maybe there was an element of that in initial variants where we were preventing infection.
We know that we did prevent infection initially, but as time has gone on as the variant new variants have emerged, then that's less relevant.
Yeah. Mm hmm. And was there extra testing done when they when when the policy of that to
inform the policy of actually introducing vaccination in school aged children.
So there was this kumquat three study we're talking about to inform which vaccines might be chosen.
We'd stopped the zero epidemiology study by that point, so we weren't continuing with that.
We there were some ongoing studies that were looking at the serology in teenagers,
both through blood tests and through saliva, just to look at how many children had antibodies.
But I think it became apparent that that wasn't all all that helpful in the
end because you could have had antibodies and you could still get infected. So you know that that in the end,
you had to be those the most effective methods of surveillance were actually the ones that were swabbing routinely and sending out,
you know, the React studies, for example, were quite brilliant, you know, in terms of just actually getting tested and the viral presence of virus.
And they were providing much more up to date and accurate ideas of infection rates in different age groups than what the serology was providing.
And I'm just. Did we finish talking about three?
How well did you notice the outcome? The four of three?
Well, the outcome of three was that, um,
this was quite an interesting one because in Concord to remind ourselves that's in 50 to 70 year olds looking at different combinations.
One combination that looked a little bit concerning or underwhelming was Pfizer, followed by Novavax.
We didn't get a great antibody response. We didn't get a T cell responses, great T-cell response.
Fast forward three. We'd already started that, started that study by the time I got that results or the design.
So there was an arm in there that was Pfizer, followed by Novavax was also an arm that was Pfizer for full dose, Pfizer followed by fractional dose.
Pfizer's get one third of a dose, which is what's used in 5 to 10 year old children.
And see how that works. By chance, we timed Concorde three to be immunising children just before the end of immigrant life.
This is I should be clear when I say children. You hold that of three.
So so in that study, as you say, we're looking at and so as it happened with this study immediately before the American way.
So whereas what it was meant to be a type of study that looked at the immune responses,
antibodies, t cells and the short term reactions, almost by chance,
it turned into what we call an efficacy efficacy study we're actually looking to see because of so many infections in that study,
you can see what was going on. And what we showed was that actually about a third of children over the whole study had infections.
A third of the 12 to 15 year olds excuse me.
And infections were much less frequent in those that had Pfizer followed by know that compared to those that had Pfizer followed by Pfizer.
And this seemed to even exceed what you'd expect for the antibody levels or T-cells.
So actually, this is and really we're the only ones that have shown this.
Actually, firstly, I think we're the only ones that have done a randomised study that it's have been across
different vaccines that has looked at efficacy and shown it in this age group or at all.
As it happens, it's in this age group.
And the so with that manuscript's been presented well that paper results have been presented in that manuscripts being finalised at the moment.
I was one of those where the results get more and more interesting as we kept going along.
So we're kind of having to adapt the study. Excuse me.
So the. So that is quite, quite strike findings as well.
Now, I think that's, you know, in some ways, again, policy has overtaken us, the world has moved on, whatever else.
So I think this is more of interested to understand why is that response.
They seem to get a much better response to that combination in teenagers compared to old people.
Why is that? We don't know. Why does that we respond?
That combination works so well in teenagers, I think is really interesting for the broader vaccines in general.
How do you know? Using an RNA vaccine followed by a protein vaccine seem to be quite a good combination.
The way the vaccine industry works is that, you know,
each manufacturer has their own product and will study that product one or two doses, whatever it's going to be.
They'll be very rare that they'll be looking to bring in mixed schedules.
Yeah, Janssen did do it for an Ebola vaccine.
That's that's not story. I've always connected.
So the so that I think is kind of passes the baton in some ways to academia or governments to actually say,
well, there is some extra benefit in potentially mixing combinations.
And so, you know,
we should keep this as an active area of research and think about how we can use vaccines
from different manufacturers in interesting ways and potentially even more effective.
So I think that's that's quite an important message that's come out of this. Mm hmm.
So you now work for Moderna. A lot of potential questions here.
Yes, I would say. Why did you move that? Now you can. That's why. Did I know what I mean?
So 19 years of one vaccine group, and that's been fascinating.
It's been interesting.
I've been involved in a lot of really fascinating and I think important research that a lot of that time I was doing half clinical,
still being a paediatrician 50% of the time and doing research and and towards the last year and a half or so,
I had to drop the clinical side because it was so busy.
So it's full time research which was okay and pity to miss the kind of, you know, bedside on the ward, hands on paediatrician role.
But I was very clear that that wasn't something I could do. Is there something for me or just on the side?
You know, I wanted to or as a hobby just to make me feel good about myself.
You know, that's such an important job that, you know, it has. It needs people who are fully up to speed.
And I felt that was increasingly becoming a struggle.
So facing career and research, then it was either I'm in my early fifties and kind of thinking, what's the next ten or 15 years hold for me?
Is it going to be continue with the vaccine group doing more of the same,
which has been great, but will be more of the same, more or less or variations on that theme?
Or is it time to make a change? In my personal things, my children just left home, so I was more free to travel and do those kinds of things,
and I knew that there was some opportunities opening up locally.
So so it's everything seem to kind of come together actually, to be honest, to say, well, this is a good time for a change.
And I would say one thing is that.
That what made a difference during the pandemic in the end was availability was obviously the lockdowns and everything else.
But we only got out of it when we had vaccines. And ultimately that came down to the manufacturers.
Sure. Absolutely. Oxford did an amazing job, the vaccine group.
But we needed AstraZeneca to get it over the line to support us and everything else.
So in the end, it was a lot about industry stepping up and making these vaccines.
So made them not for profit. So made them where they do make a profit.
But this debate to be had about that. But I think a lot of people started to look at Farmer and his friend right after that and say,
well, you know, it all impacts are made by farming, you know.
So that's what it comes down to in the end. So I found that that was quite an important way of looking at it and that, you know,
this irony technology in particular is is such an important breakthrough for vaccines.
It's a revolution in vaccines and that this has incredible potential.
My particular role is looking at using that potential to develop vaccines for children and pregnant women and against what particularly.
And so it's kind of seeing what could be.
There is clearly unmet needs. The most obvious unmet needs is what against the virus called RSV respiratory virus,
which is just overwhelms paediatric wards globally, you know, very predictably.
That's right. This this primarily affects children under one year of age, especially children in the first few months of life.
But it does cause disease, you know, repeatedly during, during childhood.
And, uh, it's associated with around 100,000 deaths per year of children under five years of age globally, which is awful.
And too many children get very sick. And another aspect with it is that in many countries, especially temperate ones, so out of the tropics,
then it comes in a very predictable spike every year so that those illnesses are concentrated over a few months.
And so you get in the winter. In the winter, it's usually automation that autumn going into winter.
And so your paediatric wards just overwhelmed.
And it is it is an awful place to be in in those wards in November where you've just got so many sick children, three month olds trying to breathe.
And and unlike most paediatric diseases, it takes days to get over.
You are used to being able to child comes in sick with a bacterial pneumonia, give them antibiotics.
They get better within a day or two. These kids can stay there struggling to breathe for days on end.
And it's it's really awful to see. So ask any paediatrician and say, what vaccine do we need?
We need an RSV vaccine. So that's one of the programs that is being, you know, RNA vaccines.
RNA vaccines definitely have potential to develop an active vaccine against RSV.
And people have been trying to make this vaccine for various various forms for nearly 50 years now, over 50 years.
And that basic research is going on both in pharma and in universities. That's right.
You know, different approaches to this. So people have been trying for 50, 60 years.
People are trying to make it RSV vaccine. There was one very early on that was disastrous.
It actually made the disease worse. And so ended up with 80% of the children that got the vaccine within.
When they then got the infection, they ended up in hospital. So it was awful vaccine and heart disease.
So different technologies were needed. This is another tool that we can use to approach that mix, you know.
So that's so long answer to say very exciting technology.
There are still some within the paediatric and maternal health sphere.
There's still important diseases where this vaccine has potential.
And so I think that's an important and exciting thing to to explore.
And what is the what's the word I'm looking for?
Environment. What differences do you find working in a commercial environment?
I know you've not been there all that long. Is it two months? Two months?
Yeah, two and a half months only. So it's really unfair to say at this point, but it has been a very welcoming environment.
Definitely very supportive. It is interesting.
Weather is perhaps more of a focus.
You know, that I think being a clinical academic is a very difficult job trying to run your clinical work alongside what is.
In my sphere, running clinical trials, so many different aspects to that and to be successful academic,
it's about having multiple grants, multiple projects going at any one time and almost the number of what you're doing, can you do more?
That seems to be the feeling all the time and to be taking on more and more.
So in some ways it's allowed me to step away from some of that.
And you know, just to recap, being a clinical academic involves clinical work, it involves teaching, it involves your research, involves your writing,
it involves all the other active academic responsibilities come with a lot of management of staff and of grants and so them administrative work.
So someone to be able to step back and actually have a bit more of a focus to say, okay,
now let's there's a very specific job that we've got to do and you're given a budget just to get on with it, are you.
Yeah, well that's one of the aspect is that I wouldn't have to control that budget directly.
For example, that's one way or another way where it's different, you know.
And so it is just a, you know, there is decisions made within the group, within the organisation and management.
The structure that will decide if a project is going to go.
And then if it does go, then you go and you have to work out what type of study you're going to do and uh, and how you're going to deliver that.
And that has been like in some ways what I've been doing for the last 20 years.
But now being able to apply it in a new setting is quite exciting.
And you know, personally or in the UK role, this is a company that has been doing most of their studies in America, some elsewhere.
And uh, and I am very keen to promote UK research the UK as a place to do this type of research.
I think we did incredibly well during the pandemic building. How important was the NHS to that?
Very so important, you know, and that builds on this kind of project over the over the last 20 years of as a, you know,
keep on going back to the main studies and then swine flu and then about which was building our capacity and and so that even the teenagers study
I was talking about 24,000 teenagers that was enrolled over 18 science and there were some in many of the sites that we then went back to to say,
can you do this COVID vaccine study.
You know, the NIH, our infrastructure, the research arm of the NHS is brilliant keeping staff in post in between grants you have.
So you've got a steady pool of nurses and doctors to draw on and and supporting it like that.
It was incredibly important. And the support that you provide during the pandemic, I can't speak highly enough of it.
So I want to to be a part of actually bringing some of of the other research that going on into the NHS.
You know, we did it for example, have not done much research on the NHS.
I know that I in in nature I know they are keen to do so.
So also so this is a good opportunity to kind of help that happen and, and I think that's only a good thing.
Yeah. Mm. Excellent. Right.
With just the last stage of this, I'd just like to talk a little bit about how the whole pandemic experience affected you personally.
And I mean, starting,
I guess with did you personally feel threatened by it by it when it when you when it was obvious that it was going to be a big deal?
You know, there was a very strange atmosphere at the start. From that point of view, I've thought about this a lot,
was we were relatively slow to introduce social distancing and and other things that society doing within the UK.
We saw vaccine, yeah, I think or medics in some ways.
You know I was at meetings in March we had.
Everyone that worked on this Oxford AstraZeneca program, the Oxford aspect, you know, 40 people in a room.
And I just hate to think what would have happened if if if it had gone through, then it was it was.
The government advice was slow. You know, there was the kind of they weren't going for a lockdown.
They're encouraging people to go to work, wash your hands.
And so I think to some extent, there was an expecting a feeling that we couldn't be seen to be deviating from that,
you know, that we were opinion leaders and that we should some extent toe the line.
But in retrospect, it was crazy that we were cramming people into a room to plan this study.
You know, we we we had so much to do in such a short period of time. We needed to get into a room to get sorted out.
And there was one meeting with all the big names, all the key people, all the administrators,
the project managers that were going to help this happen were in one room.
This was in mid-March, where code was circulating quite freely in the community.
And we were very lucky and we were very lucky throughout.
You know, we have had one close colleague who has been quite badly affected, which is which is awful.
But for during that 2020 period, there were no major outbreaks and we were very lucky amongst our staff.
I didn't feel personally, I couldn't I was still keeping my clinical work on June the 2020 and I felt,
if anything, a bit of a fraud because the paediatric wards were so quiet,
it was so minimal risk there from my interactions with patients,
minimal risk compared to my colleagues that work in adult medicine where they do have some intensive care training.
But you didn't. I was involved in intensive care and that was that was that was quite some time ago.
My clinical works as a general paediatrician on WhatsApp, so I was not spoken to until I was working on the vaccine stuff.
So that was, you know, will be considered a priority. A colleague of mine was working in the adult ward.
She picked it up very early because, you know, she was just she was dealing with mayhem.
You know, she was dealing with, you know, old people dying on the wards and not being able to give them intensive care of it.
And I think that was it was traumatic. And that and those and people being put obviously primarily of patients themselves,
but also the doctors and nurses were put into awful situations there.
So I felt, as I say, a bit of a fraud from that point of view in paediatrics which simply didn't have that experience.
I was working either on the vaccine studies or in the general paediatric wards, and that was fine.
Um, the, so that's from that personal point of view, obviously it is completely.
As expected, it is amazing to felt that whatever role to have been part of that project was incredible.
We knew it was incredibly important. It's easy to forget now that most vaccines that went into development failed.
So to have been involved with something that worked and saved 6 million lives, it's amazing achievement.
The ladies within the group and the others, you know, it was an amazing achievement.
Nothing is false. You know, there was that there was some things that you would do differently in retrospect, always.
But it was good enough that they got there.
Whereas others, you know, even the major vaccine manufacturers got it wrong, got their designs wrong, got their products wrong.
And, you know, we, we didn't we got it there, which was great. Um, there's been quite a change through the Oxford Vaccine Group, I think,
you know, people that have then seen this as well, we're never going to top that.
And so moving on to something else or even feeling perhaps, you know, they didn't quite get into it as much as they might have.
You know, they didn't have a central role in that and feeling perhaps a little bit excluded from some of that,
which also meant I think some people moved on. It's interesting,
on a side of history that you never hear is those that actually didn't quite get on
that that were left on the bench when when when the team was winning the premiership.
I think few people felt like that and moved on.
Uh. But that's you know, that's not about it is about actually in that situation,
it was just about getting the studies done in the most efficient way possible.
And that that was that was the reality of it. I think they're the main things that I'm thinking about in terms of the experience.
And where are you going into the into the office? Yep.
Through every day. Yeah, almost every day. There was a period in the.
And Winter of 2020 2021. I think we there were some brief periods where there were very high spots where we started to work from home,
but otherwise almost every day we were going in. I think that was okay.
Again, we were lucky, but in terms of getting things done quickly and so much of the work was hands on that.
And of course, yes, you had the you had the trial participants coming in.
Oh, yes. So that was part that was a big part of it. And that you wanted to be there.
As I say, as a senior person on the team, that you could give advice if there was any questions or challenges coming up,
especially when it was for the, um, for the, when the vaccine you're actually vaccinating on those days.
I mean, obviously you do any vaccinating, but I did some vaccinating minimal amounts really.
Actually, no, I didn't do any vaccinating because there were separate teams that would do the vaccinating.
And so, you know, do some hands on stuff.
I was just about to say one really genuine one of the best days of my life was the first day we recruited the Cobb clinical study.
We got going mid-February, which was the goal maybe a week later than what we wanted, but, you know,
early enough to be useful knowing that it was going to work, that we had enough interest that was.
And so I went in on the weekend and was there amongst the team, could see the amount of activity,
the amount of interest there was in the study and just feeling confident. We recorded that in ten days or something like that.
And I don't think people and my main contribution that day was it was minus three degrees.
And so I was bringing around cups of tea for everybody and bringing in oil heaters from the main building into these porta cabins.
Because the studies were being done in these porta cabins, the two mobile units, and they were freezing.
And that means they actually has an effect because it's hard to take blood if if people are cold, you know, the circulation shifts.
So so just don't bring over all these oil heaters into the portacabin and then blew the fuses.
So that wasn't so so it wasn't so helpful in the end. But I got warm enough initially that it wasn't Arctic then.
That was a great day.
I mean, in terms of satisfaction or, you know, that feeling that we were doing an important study and that that had been the winter of 2020,
there was so many periods that was stressful, 70 periods that were awful for me, actually.
My lowest point was probably going through the just before December 2020, which was great news about the vaccines was coming out at that time.
But at the moment that my task was to live the studies and I was very worried that I weren't going to work.
There were a number of things that seemed maybe to be falling apart.
Story hadn't quite delivered as I'd hoped, that had to shut down the teenager study 24,000.
I was like, Is this going to be the third or is this one going to be the one that really delivers?
And and by the end of 2020, I was very worried it wasn't going to deliver.
And then by February it was clear it was and we had it all going. So that was that was very satisfying.
Yeah. So you went through a pretty stressful period. Were there any things that you did or for periods?
Absolutely. Personally and at the wrong time, you know, it was just when the great news about the vaccines were coming out.
And for whatever reason, I was just feeling terrible. Yeah. Yeah.
And with weather and things you were able to do to support your mental health, so did you.
Yeah. Lots of walks with the dog. Yeah, yeah. It was all.
I live in South Oxford and it was all flooded. I remember it all so clearly and that it was flooded.
So it was very hard to even just get out and about, you know, it was still lockdown stuff.
So you weren't meant to be going out, you know, but you could go for a walk and to take exercise.
So family lot, lots of drives up to Bagley, which wasn't flooded.
And just every day long, long walks around, Bagley would with the family and the dogs.
I think they're just about there. Yeah. Uh. So has the.
Well, I suppose we've almost answered this,
but in what way has the experience of going through that whole period changed how you think about your work and what you ought to be doing?
Yes. So I kind of always mentioned that to be a doctor. Doctor, you know, bedside hands on and.
Having to move away from that during the pandemic has meant that actually I'm okay with that.
You know, going back to it wouldn't feel like the right thing to do now because I would have to pick it up again, I'm sure.
But actually, in some ways I think I have picked up some.
Experience of how to do these types of things.
And so I think that actually might be more useful and a better use of what I can do than being a part time paediatrician.
So that's changed that. Um, uh.
Slightly strange one bit in terms of well haven't been part of in the middle of the story like that kind of makes you look we can come.
Reflect on how others would have felt in that similar situation,
when they've also been in power of extraordinary things with extraordinary projects like that.
So perhaps it's not quite recognition that you can kind of actually think, well, wonder what that was like for them.
You know, who are the ones that felt the US here? What I'll say is that you always.
When I hear particular names associated with particular projects, you know, this project was delivered by such and such and his team.
I was like, Think about the team then rather than the such and such. Yes.
What? Who else was there and who else was involved with it and everything else,
and massive respect for those that do put themselves out to be the face of something like this.
And it was a very clear message that we had early on that interactions with the media were limited to three people Andy, Sarah and Adrian.
And I think that was very sensible. You needed controlling of the message.
You felt a bit weird being actively told. Do not talk to the media.
But in some ways I would never want to gone through what those what they went through in terms of the public, you know.
The pressure and the the the vile message they were getting, you know, the kind of awful messaging,
you know, that you're trying to kill us with these vaccines and all that kind of stuff.
And I think the scrutiny that people themselves put them that can put themselves under in those moments I think is extraordinary.
And people that can set up and can cope with that, how they cope is amazing.
And I had a similar conversation recently with someone who working with closely with Tony Tony Fauci in America.
You know, I think that was to another level. Again, it was, you know, very close with Tony Fauci.
And he was making sure that his name was on none of the publicity around this because he had his family.
He just wanted to not be caught up in that. And we were talking over didn't know about, you know, what was it that some people feel they can do that?
And I was like, he his response was Nothing I want I do not want people to know that I'm in that role.
I do not want to have that public face of this. I don't want to be the public face of the CDC for that situation.
So I think it makes me feel differently about that and some people who step up.
But the other is it's never sure. There's always big team around it, but there is something to say for those who actually will put it to the face.
To it. Mm hmm. And at the broader policy question,
do you think lessons have been learned about how decisions are taken on what vaccines should and shouldn't be used?
Well, border policy, it's clearly ushered in a new era of vaccines for vector and in particular, RNA, messenger RNA.
That's amazing outcome of this. I would hope that were a bit more flexible next time around.
We had prepared a pandemic for are we prepared for an influenza pandemic?
And we didn't get an influenza pandemic. So. From the public health messaging, public health policy.
I think that's really important that you have to look what pandemic you're getting.
And even for this year, epidemiology study will be going on given guidelines that were based on an influenza pandemic
in a yeah that and what actually more than appropriate what we were doing in the end.
So I think that's something not all. It's going to be the same and hopefully people will be more adaptable for that.
Um. A slightly cynical negative one is that lots of organisations were set up to prepare for a pandemic.
Cepi and others like that and set up this COVAX fund where people were going to share
the vaccines around globally and make sure everybody got a fair share of vaccines.
Fantastic idea. Completely agree with the intention. And it completely fell down because every country acted in their own interests.
Every country. I can see the argument it feels wrong,
but I can see the argument saying the people of Country X are elected by the government
of Country X is elected by the people of countries to look after country X.
And so they will do that. They will make sure their country gets the vaccine.
That national approach, that nationalistic approach was highly criticised and validly criticised.
But I can also I can't see how you could stop that happening unless you.
There are many more limits placed on governments and how they respond to it, and we want that as well.
COVAX was partially affected. Who said it completely didn't know it did.
Absolutely obsolete and shouldn't shouldn't be.
It was partially it did provide a lot of vaccines around the world, but not as quickly to low and middle income countries as what people thought.
There was massive vaccine inequality. Yeah, COVAX was to try to help to minimise that.
In the end, it did that to some extent,
but there was still massive vaccine inequality and governments and countries acted in their own interests and that's slightly dispiriting, I guess.
I don't see how you could stop that happening again. And I guess that's what I'm trying to say, is that's a lesson as to how to think about that.
You might well have good intentions, but how how would you lock people into actually acting through restricting supply of their own vaccines,
especially as soon as one country, of course, does it, then then it's a scramble.
And, you know, we know both America and the US and the UK were saying, yes, we will prioritise vaccines for our own country first.
So yeah, I think that's an interesting aspect of it. Going back to what you said at the beginning.
We'll have another pandemic in three years time. Oh, yes, that's right.
I think the RNA technology, the we have a great new armamentarium of vaccines that could deal with that.
And I think surveillance will be better. We'll have a pandemic scare every five years or so, whether it's a true pandemic or not.
And, you know, uh, we clearly, I think, would have to be better prepared.
I think governments know. Oh, there's just so much to that.
I mean, you can pick up so many things in terms of the behaviour of people.
I think people will pay more attention to the to the psychology of response.
People didn't think the you could cope with a lockdown and they did. Now people are very worried about that.
A lot of focus on getting enough vaccines available. And many people didn't take up the vaccines, especially in America.
What was why when it was freely available and it became how did it become a political thing when you wore a mask or got a vaccine?
Bizarre. So think more about I hope a lot of work goes into the messaging and thinking about how you avoid it becoming a political
issue again or a kind of a tribal thing about how you approach the pandemic and make it more of an all inclusive.
That's just one tiny aspect of the many, many different aspects that would need to be considered.
Are we prepared for the next one? One.
One thing we may have learnt is about the importance of just on a very specific issue, the importance of aerosol spread.
That that was played down initially and people weren't thinking about ventilation.
We all live in a medically sealed buildings now. Florence Nightingale knew that ventilation was a good thing.
We forgot that somewhere along the way and that would have been helpful here.
So I wonder if that will have a better role and may change how we think about how we design buildings.
And so we'll accept that we all get viruses in winter and that inevitable and clear messages about masks, perhaps.
Yes, that's right. Exactly. You know, thank goodness. I mean, the.
Early days of the weeks of the pandemic, we were being specifically instructed not to wear masks.
There were signs up in the corridor saying, Take your mask off if you walk down this corridor in the hospital.
I think. Yeah, said February.
March. I was seeing signs. Take your mask off.
In the hospital because they were concerned that moving from a clinical area to another one, spreading things, they had to take everything.
What kind of disrobe, if you like. And so they didn't want to see people walking around with a mask on.
That's yeah, that's just crazy in retrospect.
Now there's a message there about, you know, okay, you do need to change your clubs if you're going from one patient to another.
There's an all of that. But but they needed to go harder and faster en masse.
And it really there was a lot of this kind of.
A phenomenon that people have that, oh, well, if we get people to wear masks, they'll touch their faces more.
So that's actually going to be worse overall. And just that kind of whenever you do have an action, there may be some kind of unintended consequences,
but they're really worse than the positive impact of the action.
And a lot of people think to think to focus on the unintended consequences of any action.
If we have a lockdown, there will be a surge afterwards. If we do this, then they'll be that.
And instead of just doing the obvious thing, wear masks, stay at home.
And I think that is maybe I would hope that would be a message that sometimes the obvious things are the right things anyway.
And we'll learn more about aerosol spread and know that that's how these. That particular virus tends to spread.
We don't know for everything, of course, and that will be very important.
Early on, having proper supplies of PPE is a good start and having adequate testing capacity to be able to roll out quickly.
I hope all of those things will be ready for the next pandemic.