How computers can speed up vaccine development

Vaccines are the key to conquer threats to public health posed by coronavirus and other infectious diseases. A team at the University of Bristol, UK, is revolutionizing the way vaccines are developed, paving the way for faster and more effective vaccines.
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,” says 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.”

Synthetic particles to the rescue

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. Researchers there have developed a new class of synthetic vaccines.

“We call it the ADDomer,” says Imre Berger. The ADDomer is a synthetic particle to which harmless parts of the 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.”

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 Garzoni, director of Bristol startup Imophoron, which is bringing the technology to market.

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,” says Frédéric.

Cryo-electron microscopy

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.

Imre Berger explains: “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.”

Demanding data analysis

As a member of the research team on this project, Matt Williams 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,” continues Matt. “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.”

Broad relevance

The ADDomer technology has broad relevance, notes Imre Berger:

“We have generated vaccine candidates for a wide range of human and veterinary diseases. 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,” concludes Adam Finn. “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.”

“Research software engineering is a fairly new field that largely started in the UK and is now spreading all over the world,” says Matt Williams.

“It’s a group within a university that fills the gap between people who are experts in computers and people who are experts in scientific research. Research software engineers allow researchers to make better use of computing resources and ensure that they are best suited to the needs of researchers.”

(Story by Michelle Pauli for JISC – the article was written shortly before the current global COVID-19 outbreak, ed.Read the original article)

Published: 03/2020

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