Two women were at the forefront of the team who created the AstraZeneca Covid-19 vaccine in just ten months.
Oxford University professor of vaccinology Dame Sarah Gilbert started designing a vaccine just two weeks after reading about a mysterious type of pneumonia emerging in China.
She was joined by her colleague geneticist Dr Catherine Green who then made it in her lab.
The pair have documented the myriad of hurdles they encountered in a new book Vaxxers: The Inside Story of the Oxford AstraZeneca Vaccine and the Race Against the Virus.
Photo: © Lewis Khan
What gave them a head start in the race for a vaccine was “platform technology,” Prof Gilbert told Kathryn Ryan.
“The idea behind it is instead of developing one vaccine specifically for one disease, we develop a technology that we can use to make vaccines against lots of different diseases.
“And having worked on that for a while, we were then starting to think about what the WHO call disease X.
“And by that they meant the unknown disease, something that's going to come and start to cause illness in people, but we don't know what it is because we've never met it before. And in that case, how would we develop a vaccine against it?”
If you've have technology to make vaccines against lots of different diseases, you can in theory use it to develop a vaccine against an unknown disease, Gilbert says.
“All we need to know is the genetic sequence of the virus that's causing the outbreak and then just from a computer, we can take the information and start to design a vaccine.”
Gilbert had already been working on a vaccine for MERS which allowed her to crack on with a vaccine for this new, emerging coronavirus.
“Having worked on a coronavirus vaccine before, I knew exactly which bits of the genome we needed to know about from the new coronavirus in order to get the information and start designing our vaccine.
“Once we heard that we were likely to be getting the information that we would need we decided that we would go ahead and start straight away.”
Dr Catherine Green says the process from that point on is akin to baking. Dr Green and her team manufacture the initial vaccine, she says.
“Sarah provides us with the DNA sequence that encodes for the adenovirus vectored vaccine, which is the type of vaccine that we're making, called ChAdOx1 nCoV-19 back in the day when we started.
“We get a DNA preparation from Sarah's lab and we need to introduce that into human cells, which act as the micro factories in which the vaccine will be made.
“So, the vaccine is a self-assembling virus particle, we manufacture that in human cells and my team are growing those human cells under very strict conditions, making sure that everything's perfect, and well controlled.”
That is then grown into a “starting material,” she says.
“We think of it like a sourdough starter. It's the mother culture from that we can seed ever larger and larger manufacturing campaigns, so that we can start to manufacture sufficient material to be used in early phase trials.
“And then to go off to larger manufacturing sites for the later phase trials. And eventually, for the global deployment that's happening at the moment.”
In late March 2020, Dr Green’s team took some of that mother starter culture and started to make an actual batch of vaccine.
This is conducted under stringent conditions, she says, in a perfectly sterile environment.
“The vaccine is made inside human cells; we need to pop open those cells, extract the vaccine, which is purified virus particles, make sure there are no contaminants from that purification process, put it into the right salty water solution that keeps it stable and makes it suitable for injection into a person.
“Put it into the sterile vials, do all the testing, make sure it meets all the stringent quality criteria, and then it's ready to go to the clinical trials team.”
Prof Gilbert explains that the vaccine produces a “spike protein”.
“The spike protein is the protein that covers the surface of the virus. And that means that antibodies in the body can reach it and bind on to the spike protein and stop it being able to infect ourselves.
“So that's the one that we want to use to make the vaccine, but we don't want the rest of the coronavirus, just the spike protein.”
The genetic sequence of that spike protein is then synthesised to produce am adenovirus which is then injected into someone’s arm, she says.
“The adenovirus will go inside cells and that will start to make lots of lots of copies of the coronavirus spike protein. And then that stimulates the immune system, because what the immune system does is all the time it's looking out for something different, something foreign, and then it will react to it.
“Because the spike protein is new, we start to get an immune response against that spike protein. But the adenovirus can't spread in the body, it's been modified, it's been made safe.”
This means that in the future if someone is exposed to the coronavirus they have an immune memory, she says.
“They've got the antibodies to make a quick response against the coronavirus to stop it from causing illness.”
The first part of the programme was academic lead, while AstraZeneca had the expertise to scale things up, Prof Gilbert says, and Dr Green says by this time the workload was intense.
“The pandemic was growing and the data was worse every day in terms of number of people infected, number of countries which were being affected and at home by March we were in lockdown, as you guys were, and our lives were affected.
“So, you're suddenly having to do what you know how to do, we have the expertise to do this, you've done it many times before, but we've never had to do it at this speed before.”
Working with a large pharma partner was also a new experience, she says.
“We had a big pharma partner on board who were fantastic. But we had to learn a lot about them and their ways of working and adapt them slightly to our ways of working.
“In the book we kind of describe it like we’re the family run pizzeria, where we do everything ourselves. We buy our own ingredients, and we assemble the pizzas and we do the publicity and put the leaflets through the doors and deliver the pizzas.
“But, AstraZeneca have systems and logistics. And we had to learn a new language and a new way of working in order that we could work together.
“But I mean at the end of that, I think we came to a really productive way of doing innovative science.”
The research team reported to the media their progress, which was encouraging but the results were complex, Prof Gilbert says.
“We did have to explain complex results and it's not always possible to explain complexity immediately.
“Sometimes it takes a bit of time to develop more understanding. And we were, I think, being accused of lack of transparency, whereas the reality was that we were reporting what we knew and there wasn't any more that we could say about it.”
Describing that complexity was one of the motivations for writing the book, she says.
“And we don't feel that you can necessarily get all that complexity across in in a very short article, it takes a bit more time.”
The risk of blood clots is addressed in the book, she says.
“We all happily get into a car, to drive to work or to drive to see family, but actually quite a lot of people die in car accidents on the roads every year, travelling by car is absolutely not risk free.
“More people are concerned about travelling in aeroplanes than they are in cars. But actually, air travel is very much safer than traveling in a car, whether you look at it in terms of time spent, traveling or distance travelled.
“So, we're not always very good at making sensible assessments about risk, we tend to dismiss things as being something we don't need to worry about, or else something that we're really very worried about, without necessarily understanding the level of risk in each case.”
The risk of blood clots with the AstraZeneca vaccine is very low, she says.
“The risk is very low and it's also less in older people than it is in younger people. And of course, in older people the risk of being infected with Covid is very, very much greater.
“So, this enables the regulators and the policymakers who recommend which groups should be given the vaccine to make their recommendation to use the vaccine in older people where the risk-benefit ratio was very much in favour of them receiving the vaccine, whereas in younger people who had less risk from covid, and slightly more likely to develop blood clots, and it was a different balance of risk and benefit.”
Dr Green wanted the book to bring not just the science, but the people doing the science to the forefront to ally people’s fears about the speed of the vaccine’s development.
She had an encounter while on holiday in Wales that demonstrated such fears.
“A lady in the queue for pizza in front of me was saying to her friend that she was concerned about the vaccine because I think basically she didn't know what was in it, she felt that ‘it’ had been made by ‘them’ an other, some kind of global elite who she doesn't necessarily trust.
“And I think that was part of the trigger for us in writing this book. And one of them was to find a way to explain within the context of who we are, that this is our job, and this is our life and we are experienced and expert, but we are also academics with a public health remit we're not a global pharma consortium.”
