00:00:03:00 - 00:00:24:17
Irene Tracey
Well. Hello everybody, and welcome back to the next episode of Fire and Wire. I am delighted to be joined today by three wonderful people who have been at the forefront and continue to be at the forefront of our vaccine program. And let me start by, first of all, introducing my three guests. We have Professor Dame Sarah Gilbert, who is the Said Professor of Vaccinology at Oxford's Nuffield Department of Medicine.

Irene Tracey
You will remember her name was all over the media at the time of the pandemic and she is, of course, internationally recognised for her work on viral vector vaccines and the leadership she took in developing the Oxford AstraZeneca Covid 19 vaccine. So welcome to you, Sarah. We also have Professor Maheshi Ramasamy, who's from the Oxford Vaccine Group. She is a clinician scientist in the Oxford Vaccine Group, and she specialises in adaptive immune responses and leads clinical trials focussed on enteric infections.

Irene Tracey
And we're joined by Associate Professor Sam Vanderslott, who is an associate professor in the Pandemic Sciences Institute. Sam leads the Vaccine and Society Unit, here in the Oxford Vaccine Group. So again, a really important area where we can again understand a little bit more some of society's hesitations and worries around vaccines. So welcome to you all.

Irene Tracey
Thank you all for taking time. I'd like to find out a little bit, sort of what drew you into the field. But before we get there, you know, we obviously did this amazing thing in the pandemic. Why Sarah is Oxford so good at this? You know, we do have extraordinary depth and breadth. And I know that we've sort of invested in it over the years.

Irene Tracey
But why do you think Oxford was able to step up at pace and help the world at that time?

Sarah Gilbert
So what was different about Oxford compared to many other academic institutions around the world is the the breadth of research that we do and the fact that we do translational research. So we're academics. We like to find out how things work. We like to understand disease. We like to understand the pathogens. We like to understand how the immune system works to defend us against those pathogens.

Sarah Gilbert
But we're also working on how to work with the immune system to make the vaccines that train the immune system to help us respond to diseases when we actually encounter them for real. But we don't just understand how this might be done. We actually make vaccines. We produce things, we test them in the laboratories.

Sarah Gilbert
And then, very unusually, we have the capability to produce vaccines to very, very high regulatory approved standards in our GMP. So that's Good Manufacturing Practice production facility, which is approved by the regulators to make vaccines that we can then use in our clinical trials. And just across the road from our manufacturing facility, we have a clinical trial centre where we can start to test those vaccines for the first time.

Sarah Gilbert
And we would always start with young and healthy people. And then gradually we expand the numbers, we expand the age range, and we can start to look at not only are these vaccines safe when we give them to people, are they giving us the type of immune response that we expect to be protective? And in some cases, we can also then go on and test, do these vaccines actually protect us against the diseases? So do they work? And we can do all of those steps within the University. And that's the part that's very unusual.

Irene Tracey
Yeah. No, it's extraordinary. And it really is that sort of bench to bedside that people do hear about. And although we have that, sort of, in a few other areas, not maybe at the scale with the critical mass that you've got and the speed at which you're able to do it, because you've really coordinated it geographically, actually, on one side -

Sarah Gilbert
We did, and obviously we have partners. AstraZeneca was a hugely important partner for us in the pandemic. What they did was take on the responsibility for manufacturing all of those doses of vaccine, and that's a large part of the reason why the vaccine had so much impact, why it saved so many lives and it's saved so much money around the world, because AstraZeneca made so many doses available.

Irene Tracey
And sort of on the clinical side, because obviously you're clinicial, Maheshi, do you think the the ease with which you can take the discovery biology into the patient, you know, as Sarah was just detailing, you know, is that something that is, you see attractive for people wanting to stay and finish their clinical training with us or come and work with us?

Maheshi Ramasamy
Absolutely. We have a great clinical trials unit set up within Oxford. And within vaccines, we have the ability to do early phase clinical trials. So testing vaccines for the first time in humans, all the way up to sort of phase two or phase three studies where we test vaccines in different age groups and people with different conditions, as well as looking for efficacy.

Maheshi Ramasamy
The other thing we do for some diseases is that we have, controlled human infection models. These are a really novel way of testing whether or not a vaccine works. So normally with vaccine efficacy studies, as we saw for Covid, you need large numbers of people involved in clinical trials, tens of thousands of people. And it takes time to accumulate the data to see whether or not the vaccine protects you from disease or not.

Maheshi Ramasamy
And that's not always feasible for rare diseases or diseases that are common in low and middle income countries. So within Oxford, we have developed this tool of the controlled human infection study, where we take healthy volunteers. Of course, we consent them fully, and then we carefully expose them to a controlled amount of a bug.

Maheshi Ramasamy
So that could be something like malaria. It could be something like the pneumococcus that causes pneumonia, or it could be, something like typhoid, the bacterium that causes enteric fever. And so we give them a very careful dose of the pathogen, of the bug, and then we follow them. Really carefully. We do lots and lots of tests for microbiological endpoints as well as immunological endpoints.

Maheshi Ramasamy
And then we know exactly when when they start to develop disease. And then we go in and we treat them as needed. And this is a very powerful tool, then, to test vaccines in a much smaller number of people than you would have to do with an efficacy study. So we demonstrated this, for example, with our typhoid conjugate vaccine studies.

Maheshi Ramasamy
And the idea is that you take, say, 100 people, 50 of them would have a placebo vaccine, 50 of them would have full investigational vaccine. And then after about a month, you challenge them all with typhoid bacteria.

Irene Tracey
How are you guaranteeing that for the group on the placebo arm, they're not exposed to a dose that's really going to cause some problems?

Maheshi Ramasamy
We sort of start low and then we sort of use gradually increasing doses of the bug. And it's a bug that we know. We know exactly the nature of the bug. We know the genetic sequence of the bug. We know whether or not, for example, it's resistant to antibiotics or not. And we know exactly what to watch for.

Maheshi Ramasamy
And we monitor all our participants very, very carefully.

Irene Tracey
Okay. Well, look, listeners volunteer, please. We need always human volunteers. Sam, let's come to you. I'd love to know just what your journey was to becoming an associate professor in the Pandemic Sciences Institute. And what sort of drew you into the field?

Sam Vanderslott
I sort of took a bit of a tour of the social sciences, I did an undergrad in economics and then did politics and, did my PhD in something called the Sociology of Science. And there I could have really picked a lot of different science topics that affect society. What I ended up doing my PhD on was about neglected tropical diseases. During that work, it made me think about what brings attention to topics, of research in health, and that affect society in a big way. And, and vaccines did come up as a topic that I'd like to start working on. And it was a real contrast to then work on a topic that does get a lot of attention. But I've, through my research, have been also interested about how you encourage pro-vaccine attitudes and behaviours.

Sam Vanderslott
And that's been my concentration over the last few years.

Irene Tracey
Why don't we just get into that, you know, and, and maybe before that, you know, so you can just remind us just how bleak it really was in the pandemic times. So I think we have blanked that out. And just what a get out of jail card it was when you guys produced that vaccine.

Sarah Gilbert
Obviously we're all very keen to move on from the pandemic. There were so many negative aspects to it, but one of the things that we've really forgotten about, and to be honest, a lot of people didn't really see in detail, was the impact that this disease was having in hospitals, particularly the the middle and the latter half of 2020, where we had many, many people in intensive care units on ventilators and it was not possible to save all of their lives and people were receiving the best treatment possible, therapeutics were being developed, so treatment was gradually improving, but people were still being made very, very sick by this disease and dying in very sad circumstances. Because the measures we had to take to try to prevent more people being infected meant that people couldn't be with their loved ones. And what happened when the vaccine started to be rolled out from the very, very end of 2020, more the beginning of 2021, we saw roughly equal usage of the UK of our adeno vectore vaccine and one of the mRNA vaccines, we were able to see by March that lives were being saved.

The death rate in people over the age of 80 who had just their first vaccination was decreasing rapidly. And that very, very quickly started to have a major impact on the hospitals, on the NHS.

Sarah Gilbert
And it started the process of gradually being able to return to normal and, and think about other diseases that need to be treated, which were obviously being neglected during the pandemic. And I've had so many words of thanks from people who worked in the hospitals, in the intensive care units at that time who've said, it really changed our lives when these vaccines became available.

Sarah Gilbert
It made such a difference, and we we tend to forget about that, and we tend to look back and think, well, did you know, 'did I really need the vaccine?'

'Was it that bad?' But actually, across the board and particularly in the hospitals ee really, really did.

Irene Tracey
Yeah. Maheshi, you want to say something...

Maheshi Ramasamy
Just to kind of give my own personal reflections on that. So I'm an infectious diseases physician. So I was very much at the frontline throughout 2020 and 2021. And I have this really clear memory of this one evening in December of 2020 when, you know, we were on take, we just admitted, you know, 30, 40 patients with Covid 19.

Maheshi Ramasamy
All the ITU beds were full. And then I admitted this young woman who was pregnant, she was gasping for air. She was on the maximum amount of oxygen that she could have. And then the oxygen supply in the hospital ran out. And one of my resident doctors turned to me and said, is this what the end of the world feels like?

Maheshi Ramasamy
And it really did feel like that. And people have really forgotten what that was like. And what changed that was vaccination. I'm working clinically this month and winter viruses are on the rise again. But actually, you know, the hospital is a completely different place to the way it was in 2020. And it's really important that we don't forget that. This is one of the problems of the success of vaccination, because we don't see the worst of those diseases.

Maheshi Ramasamy
We don't see measles, we don't see tetanus, we don't see polio. We don't- we've forgotten how bad they were.

Irene Tracey
Yeah. You're absolutely right to remind us, and I'm so grateful and just thank you on behalf of everybody, you know, again, for the work that you all did in the NHS. So, Sam, I come back to you. Why do we have such a problem? What is it we're not doing right? Because it does strike me, listening to the media, that more and more people don't want vaccines.

Irene Tracey
And is it that we just haven't communicated? We're not reminding people? We don't want be all doom and gloom all the time, but maybe we do need to be more effective with the comms and just to remind people about what life would be if we didn't have it.

Sam Vanderslott
To reflect on what Maheshi just said. It's actually the older age groups that do remember these diseases so they can be more easily persuaded. Some of the younger generations, they haven't experienced the diseases that we have vaccines to protect against, and there needs to be different ways of explaining the benefit of vaccination and going into communities, especially where there have been quite a high level of distrust of the government of, of health authorities and experiences with the health system that might have been negative.

Sam Vanderslott
These all affect whether someone's willing to take a vaccine. The groundwork really needs to be laid outside of pandemic times. We can't expect communities to be trusting of a new vaccine, especially in a short period of time, without any relationship building and without any work on that communication and engagement beforehand.

Irene Tracey
How helpful or unhelpful is the media in all this?

Sam Vanderslott
In general, the mainstream media has been quite supportive of vaccination and a lot of the policies of the typical media outlets, like the BBC, is not to provide a false balance. But on the online sphere and social media, it is a free for all. So, there's not the same kind of barrier to entry that you would get, in more established news outlets.

Sam Vanderslott
And this is where a lot of people are getting their news and information from. So we do need to be carefully looking at what sort of misinformation is out there on social media. How to identify that, how to address that, and to also provide places where people can go and find information that they can trust. And that's credible.

Irene Tracey
The spread of disinformation and misinformation. It's a real challenge. If you're a young parent and you want to do the right thing by your child. It is, again, we've got to put ourselves in the shoes of somebody. It's very difficult to navigate this complete deluge of information, sometimes from authorities. And so how do we really, yeah, combat that. Your clinical colleagues over there, how are they managing at this point in time?

Maheshi Ramasamy
So it's really interesting. The UK Health Security Agency runs an annual survey looking at parental attitudes to vaccination. And actually we're not doing too badly in the UK. So, you know, a couple of years ago when the sort of high 90s in terms of parents thinking that vaccines are safe and effective and good for their kids, and we're probably in the high 80s at the moment, so kind of you know, a little bit worse.

Maheshi Ramasamy
But overall, people, parents, you know, are keen to have their kids vaccinated. But, you know, and the people that they trust, interestingly, are not social media in these surveys, they are actually, the health care workers. And, and I think that's really important because health care workers are - they're not pharma, they're not the government,

Maheshi Ramasamy
they are kind of, you know, professionals. And so they are trusted to kind of give good immunisation advice. But we've seen a real fragmentation of health services in the UK, over the last decade or two. So, for example, you know, in the late 90s, we had these Sure Start Centres where kids would see the healthcare workers and they would be see healthcare assistants and getting their childhood vaccines.

Maheshi Ramasamy
And because of years of austerity that's actually gone now. So we don't have those interfaces, particularly in difficult to reach communities or in people who don't necessarily seek healthcare. We've lost some of those interfaces with the communities. So I think, you know, it's not just addressing social media, it's providing the the logistical support to get kids vaccinated and to offer vaccination to hard to reach populations.

Sam Vanderslott
I bought my one year old son for his vaccines, a little while ago. And the nurse there had said, oh, right, there's a lot of vaccines, I'm really sorry, I don't know why we have to have so many vaccines. I had to really bite my tongue, but I did say it's all right, well, I actually do. I do want these vaccines.

But I could see that there also needs to be better training and support for healthcare workers who are on the frontline, who will have the more difficult -

Irene Tracey
The fielding...lots of really probably quite challenging questions. Yeah, yeah. And that's not fair on that individual is it. Because it puts them in a very uncomfortable position. As you were saying, Maheshi, what drew you into the field then? I mean, you could have gone many different ways, I guess, with your training and background. What was it that drew you into infectious diseases?

Maheshi Ramasamy
Well I grew up in Sri Lanka. And so when I was a teenager and I was shadowing doctors and things, the stuff that I saw on the wards was all dengue and malaria and Japanese encephalitis. So I kind of thought that's what medicine was. So I've always been interested in infection. You get a little bit less of that in the UK, I have to say.

Maheshi Ramasamy
And actually I was really lucky. When I was an undergraduate, I worked with a fantastic scientist called Professor Margaret Stanley, who developed the human papillomavirus vaccine, which, as you know, is now widely used around the world and has probably saved millions of lives from cervical cancer. And so I've always been interested in the idea of using vaccines to stop infection in the first place, to kind of put me out of my day job as an infectious diseases physician.

Irene Tracey
That would be the sign of success, that you have to retire early, and rightfully so. Sarah, did you have an inspirational role model that drew you into science and then into this particular space?

Sarah Gilbert
I don't actually have a role model. I'm often asked, you know, who was your role model? But it was actually science itself. Yeah. It's understanding, how things work and then how we can use them to make our lives better. That's really, was always my motivation. I originally did microbiology and biochemistry for my undergraduate and then my PhD.

Sarah Gilbert
And I ended up working in a biotech company where we were making blood proteins, human blood proteins produced in yeast that we could purify. And this was working towards making artificial blood. Then I thought, I wanted to get back into academia again. So I came to Oxford, not to work on vaccines, but to work on understanding the interactions between the host and the parasite in malaria infections and how the genetics of each interact.

Sarah Gilbert
But that very quickly led to an understanding that there was a way that we could use this information to help us develop vaccines against malaria. But I moved on to thinking about vaccine technologies, ways of making vaccines that we could use to make lots of different vaccines. And that's really important when we're thinking about the viruses that cause outbreaks, because the sooner we can respond to an outbreak, actually the fewer people we need to vaccinate.

Sarah Gilbert
And that's really the aim, to be ready, to control an outbreak as soon as is identified, to shut it down. That protects the rest of the world. And we don't need to vaccinate everybody the way we did against COVID.

Irene Tracey
If the world knew what you know. I don't know how you sleep.

Sarah Gilbert
What we really should be doing is being ready, because the more prepared we are to act quickly, really, the less impact there is of any of these outbreaks. And what's happening now in this field is that, we are trying to identify all the different types of viruses, all different families of viruses that might cause an outbreak and making sure we understand how to protect us against each of those different families of viruses.

Sarah Gilbert
A big problem we had in 2020 was that we discovered it was a coronavirus that was causing the the epidemic, which became a pandemic. And we don't have any vaccines against coronaviruses for humans. So we didn't really know what we had to do if it had been a very close relative of, for example, influenza A, we know how to make flu vaccines.

Sarah Gilbert
So that would have given us a lot of very useful information, but a virus from a different family - that gave us a big problem. We don't want to be in that situation again. So even if it's a slightly different coronavirus that was to cause an outbreak next time, we know what works, we know where are we going to start from and likely where are we going to end up. So we're much better placed. And we need to do that for all the different virus families. So that's a big aspect of what I'm working on now.

Irene Tracey
That's fantastic. And none of this can happen, of course, without funding. And, you know, mindful that recently we've been very fortunate, we've had big dollops of great research partnerships, you know, given to our efforts, you know, whether that's the cancer prevention programme with GlaxoSmithKline or with our relationship with the Ellison Institute of Technology in again, the sort of human challenges work.

Irene Tracey
But there's been other funding as well. And maybe I could just finish by, you know, asking you each to comment a little bit about the importance of funding and those partnerships as well, and the collaborations that's so key for all of us to do our work.

Maheshi Ramasamy
It feels like this is a really tricky time for global health research and for vaccine research in particular. And there are, because of, you know, economic reasons, there are sort of likely to be cuts to big bodies like the Coalition for Epidemic Preparedness and Innovation, which fund outbreak pathogen research, cuts to funding to organisations like Gavi, which are responsible for distributing vaccines to low and middle income countries.

Maheshi Ramasamy
And then also, you know, cuts to things like mRNA vaccine research in the UK. We've seen that with the, with sort of BARDA (Biomedical Advanced Research and Development Authority) funding cuts as well. So I think it's important for us to kind of, you know, be real advocates for the importance of vaccination, not just, you know, developing new vaccines for bugs that we haven't got vaccines for, but also for getting vaccines into arms.

Irene Tracey
Well said, well said. And Sarah, how about yourself?

Sarah Gilbert
So I would like to take the opportunity to thank the marvellous philanthropists who funded us during the pandemic and after the pandemic, and people have supported us, small amounts and large amounts, and we've been extremely grateful. And one of the reasons this is so important is it really enables us to respond quickly. But then for some of the late stages in vaccine development where we have very good early results and we need to get these vaccines through regulatory approval so that they can be used when there's an outbreak.

Sarah Gilbert
Those trials that we need to do, the clinical trials can be pretty expensive. We need to make sure that we're doing the right trials, who's doing them in the right way. But we also need a lot of funding to do them. And that's where the Coalition for Epidemic Preparedness Innovation, or CEPI, as it's known for short, that's where they come in and they support this kind of work, and they receive funding from many governments around the world.

Sarah Gilbert
And the Wellcome Trust gives them funding as well. But we couldn't do the very late stage development, which frankly, is quite expensive. But absolutely essential. We couldn't do that without CEPI.

Irene Tracey
Yeah. No. Well said and well said for, you know, the philanthropy. I mean so much of our work in Oxford and just Oxford to stay standing frankly, couldn't happen without the enormous generosity of alumn and non alumn who support, you know, the brilliant work that you do and the excellence in the University. I'm hugely grateful, as you say, just being able to not have to go through the long grant cycle and just do it and test, that idea's essential, isn't it, to keep going?

Well, we've come to the end of our time, sadly. But thank you again to all of you for everything you've done. You know, my goodness, in at that time, but for all the extraordinary trials that you're running at the moment and the work that you are doing to help, again, make sure that we're protected against some of these very common and old infections that we still haven't quite got our heads around let alone the new ones that are breaking out.

Irene Tracey
And to Sarah, again, just on behalf of everybody, thank you for everything you did for us in the pandemic. You know, I know you've been thanked many times, but it goes without saying, you know, we're so, so proud of the vaccine work that goes on in Oxford. And we owe you an enormous debt of gratitude. All of you, for everything you did to get us through that period of time.

Irene Tracey
So without further ado, I'd like to thank Professor Dame Sarah Gilbert, Professor Maheshi Ramasamy, and Professor Sam Vanderslott. Thank you so much for joining me and keep up the great work. Thank you, thanks.

Maheshi Ramasamy
Thank you very much.

Irene Tracey
I look forward to joining you for the next instalment. Take care and thank you.