University of BristolBlue-sky thinking about vaccine development

Blue-sky thinking about vaccine development

University of Bristol

High-performance cloud computing is laying the foundations for new types of synthetic solutions

Vaccines, one of the most effective weapons in the fight against pandemics, create immunisation against diseases such as measles, pneumonia and polio and prevent 2 million to 3 million deaths a year, according to WHO statistics.

Thanks to a team of researchers from the University of Bristol and the National Centre for Scientific Research in Grenoble, that number could rise further. The researchers have made a huge breakthrough by creating a new type of vaccine that can be produced quickly and at large volumes, and can be stored at room temperature – which could lead to the first-ever vaccine against the mosquito-borne Chikungunya virus. As yet, there is no way to inoculate against this infectious disease, which is typically found in sub-Saharan Africa and causes headaches, vomiting, joint pain and even death.

The international team has combined cryo-electron microscopy, synthetic biology and high-performance computing to model and create a Chikungunya vaccine candidate. And not before time – the virus is spreading as climate change and deforestation drive mosquitos out of their natural habitat, leading to outbreaks in the United States and Europe.

“I think this is a good example of how modern science is done – you’ll rarely do this by yourself in your own lab,” says Christiane Berger-Schaffitzel, a professor of biochemistry at the University of Bristol.

The vaccine candidate uses a synthetic protein particle called ADDomer, which resembles a virus but contains no genetic material – making it a safe way to deliver the vaccine. The researchers have engineered its surface to resemble Chikungunya “epitopes”, the parts of a virus that dock with human cells and trigger the body’s immune defences.

But what Professor Berger-Schaffitzel says is “quite exceptional” is that the particle is stable at room temperature. Normally, vaccines must be refrigerated to remain effective.

“That’s very important for a vaccine, especially when we talk about tropical countries and tropical diseases like Chikungunya. You want the particle to be able to survive disruption in the cold chain,” says Professor Berger-Schaffitzel, who is examining ways to make the particle even more temperature stable and cheap to produce.

“We want vaccines to be affordable for all people,” she says. “This is one of our key interests in vaccine development: to produce new vaccines in a safe, efficacious and cheap way. It adds to the cost when you have to have a cold chain, because if the vaccine gets warmed up, it stops working and you either have to throw it away, making vaccination more expensive – or if you do still use it, people aren’t really vaccinated.”

To validate their design, researchers in Professor Berger-Schaffitzel’s lab have used cryo-electron microscopy to visualise and model the ADDomer particles. The microscope takes images at atomic-level resolution, which are used to create highly accurate, 3D digital models.

This process can take a long time and is “very computation-intensive”, Professor Berger-Schaffitzel says. The team, therefore, began working with cloud technology leader Oracle to speed the process through its high-performance computing infrastructure.

“It generally takes months, sometimes years, for universities to procure the hardware and software needed to process such large volumes of data, which needs to be done even before experiments can begin,” Professor Berger-Schaffitzel adds.

Bringing in high-performance computing capacity meant the researchers were able to do this in a matter of days. Because the Oracle technology is cloud-based, the team has immediate access to several types of computing resources, which they can use as needed at each stage of the process. First, a large volume of data from the cryo-electron microscope must have a series of computationally expensive processes applied to it – to build first a 2D, then 3D model, then remove thermal noise, and then to analyse the 3D model.

“Reducing the time needed to take the data from the electron microscope and come up with an accurate model of what the underlying virus, bacteria or the drugs or vaccines being used to treat them are, is a critical part of the process,” Professor Berger-Schaffitzel says. “And if you can accelerate that process, it means we can effectively bring drugs and vaccines to the market more quickly.”

The ADDomer particle has shown promising results in animal studies, and the researchers are optimistic that it could lead to an effective Chikungunya vaccine that, thanks to its temperature stability, can be transported and stored cheaply.

Imophoron, a start-up company founded by researchers working on the project to further develop and commercialise ADDomer, will soon carry out pre-clinical trials on the vaccine.

Imophoron will also work to use the ADDomer scaffold to manufacture vaccines for other diseases. Professor Berger-Schaffitzel says the team has already had promising results generating epitopes for the Zika and Gumboro viruses.

It may even be possible to use the approach in future cancer treatments, she says. “If you know what’s mutated on cancer cells, you could also direct the immune system to recognise cancer cells as aberrant cells and try to kill them,” she explains. So far, the team has modelled epitopes for melanoma.

None of this could have been done in isolation, she explains. “Modern science is highly interdisciplinary and highly collaborative, and this is probably one of the prime examples demonstrating two companies with different expertise coming together to accelerate scientific discovery at my lab.”

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