A team at the University of Bristol is revolutionising the way vaccines are developed, paving the way for faster and more effective vaccines against diseases for which there is currently no means of prevention.
The scientists at the heart of the project explain how the Research 4.0 tools of big data and cloud computing are changing the way they engineer vaccines – and protect everyone from viruses.
“Half a century ago, many people started to think that infectious diseases had been solved. And we were totally wrong. Infectious diseases have never been more of a problem than they are today.”
That’s the stark warning from Adam Finn, professor of paediatrics at Bristol Children’s Vaccine Centre, University of Bristol. He explains:
“As you conquer some problems with infection, others come up to replace them. And the drugs that can treat these infections stop working as the organisms learn to be resistant to them.”
But there is an answer: vaccination. It is “our most successful defence against infectious diseases,” according to Imre Berger, professor of biochemistry at the University of Bristol and the director of the Max Planck-Bristol Centre for Minimal Biology.
The fridge problem
However, vaccines do not travel well or last long, particularly in warmer parts of the world.
“A major problem with vaccines at the moment,” says Imre, “is that they need to be refrigerated for storage and for transport. Otherwise they become inactivated.”
“And a fridge needs a power supply,”
“So while you might be able to reach any part of the world with a bottle of Coca-Cola, being able to reach any part of the world with a refrigerated vaccine is really quite a challenge. And without effective monitoring you may end up giving ineffective vaccines to children and then the vaccine gets a bad name even though there was nothing wrong with it. What was wrong was your cold chain.”
Then there are the diseases for which there is no prevention, such as Zika and chikungunya. These mosquito-borne diseases were previously confined to sub-Saharan Africa but, because of global warming and climate change, the mosquitos that carry them are travelling further afield, to Europe and the US. There is currently no vaccine against chikungunya.
Not yet, anyway. But the answer may well lie in the latest iteration of engineered vaccines that are now being developed. They might yet tackle many of the challenges posed for centuries by the traditional vaccines that trace their history back to the original smallpox vaccine, invented by Edward Jenner in 1796.
New class of vaccines
“We have developed a new class of synthetic vaccines. We call it the ADDomer,”
says Imre. The ADDomer is a synthetic particle to which harmless parts of the chikungunya virus can be added, to fool the immune system.
“When the immune system sees it, it develops antibodies against it, which will protect when the real virus arrives.”
“This technology is unique because it doesn't rely on a cold chain,”
says Frédéric Garzoni, director of Bristol startup Imophoron, which is bringing to market the technology underpinning the ADDomer development. Adam agrees:
“You can engineer it to be very stable and we need vaccines that will survive in hostile environments.”
In addition, says Frédéric,
“we can mass produce it at low cost, which is basically ticking all the boxes.”
Another benefit is the potential for speedy development.
“One problem today is that it could take six to nine months to produce a vaccine,”
says Frédéric. So by the time a vaccine is ready to meet one winter ‘flu, a different virus strain is on its way for the next winter. But the purely synthetic ADDomer can be produced more quickly and without the present-day risk that the vaccine itself might mutate during production.
“We know what we are producing and we know which product we're going to have at the end. We can produce quite fast.”
Big picture, big data
What makes ADDomer possible today is the way researchers can manage big data through fast, high-volume cloud computing and fast, high-volume connectivity to transport the data to the cloud.
“We had to know the structure of the ADDomer at near-atomic resolution. This we determined by cryo-electron microscopy. This was a first. Cryo-electron microscopy yields literally thousands and thousands of images of your particle. By combining these images from all conceivable orientations, you can calculate the structure.”
Dr Matt Williams, research software engineer at the University of Bristol, takes up the story.
“You need lots and lots of images because each image is quite fuzzy and noisy but by using very advanced reconstruction software packages to align, classify and then reconstruct, we were able to get a full 3D model of the particle at a far higher resolution than was ever available previously.”
High-speed cloud connections
As a member of the research team on this project, Matt was asked to find a way to take the large data volumes collected on the microscope, use the cloud resource provided and put them together into something that could support the demanding data analysis.
“The software we created for this is called Cluster in the Cloud,”
“It allows anyone with access to cloud resources to create a very familiar software environment but fully based in the cloud, making the best use of cloud facilities and cloud technologies.
“For that, Janet was really useful. It provides a very stable, high speed connection to the cloud providers. If we hadn’t had access to the high-speed Janet Network, I think the real constraint it would put on us is that we would have to use smaller amounts of data in our analysis, which would have resulted in a lower resolution. We wouldn’t be able to do our jobs.”
A step change
Looking forward, Imre expects ADDomer technology to tackle far more than just the chikungunya virus:
“We generated thirty other different vaccine candidates for a wide range of human and veterinary diseases, to demonstrate that our approach is not confined to chikungunya alone. In the future we will pursue the most promising candidates and we are very interested to see how powerful our technology really is.”
“I think this is a step change,”
“It's a proof of principle. Until now we've had to accept the materials that biology gives us, that microbes make when they make themselves. This represents a more deliberate attempt to actually engineer the bits and pieces that you need to make a vaccine work.”