Scientists use new technology to develop a path for a novel synthetic polio vaccine

Includes a combination of X-ray crystallography and electron cryo-microscopy

David Stuart holding a sculpture of the hand, foot and mouth virus, a childhood disease that infects 1.6 million people each year. Stuart solved the structure of the virus at Diamond Light Source and has since created a potential cure for this currently untreatable disease. His work may also lead to new treatments for other diseases, such as polio. (Copyright: Max Alexander/Diamond Light Source)

Scientists from the UK and US are using technology that helped in the design of a new synthetic vaccine to combat the foot and mouth disease virus (FMDV) to target the virus that causes polio.

The synthetic vaccine, currently being engineered in collaboration with Professor Dave Rowlands at the University of Leeds would provide a powerful weapon against polio. The project is being funded by a £438,000 grant from the World Health Organization and the Bill & Melinda Gates Foundation.

The team hopes to create a vaccine that does not contain the viral genome but instead ‘mimics’ the structure of the live virus. Such a vaccine would be quicker, easier and safer to produce, they say. Even after the apparent global elimination of poliomyelitis it will be necessary to continue vaccination as a precaution against reintroduction of the virus from hidden sources, such as rare chronically infected carriers. A synthetic vaccine would fulfil this role without the inherent danger of accidental release of virus associated with the production of current vaccines.

Speaking at the American Association for the Advancement of Science (AAAS 2015) meeting in San Jose last week, Professor Dave Stuart, Life Sciences Director at Diamond Light Source, the UK’s national synchrotron science facility, and Professor of Structural Biology at Oxford University, said: 'Using a combination of techniques, including X-ray crystallography at Diamond and electron cryo-microscopy in Oxford, we’ve begun the task of gathering crystal structures and electron microscopy images that will tell us what we need to know to stabilise the shell of the virus and engineer a strong vaccine that has the ability to bring about the desired immune response in humans.

We’ve begun the task of gathering crystal structures and electron microscopy images that will tell us what we need to know to stabilise the shell of the virus

'Following on from the success we’ve had with the foot and mouth disease vaccine, we aim to transfer the approach to vaccines for other viruses including polio. Early results with polio are very promising, with synthetic particles being produced and evidence of successful stabilisation.'

Prof Stuart has devoted his career as a structural biologist to outsmarting viruses to benefit human and animal health. 21st century technology will, he believes, play a key role in helping us dramatically to improve our response times when new virus outbreaks occur.

Radius coloured surface representation of Type 1 poliovirus (Mahoney) (PDB ID:1HXS, DOI:10.1006/jmbi.2001.4485). The surface is coloured from blue to red according to the distance from the particle centre. (Courtesy of Dr Liz Fry, Dept. Structural Biology, Oxford University)

He added: 'Our basic research capabilities are being greatly enhanced by developments in a number of key areas such as synchrotron light sources, light microscopy and the now fantastically powerful electron microscopy technique.

'Using the latest technology, we can engineer vaccines that are billions of times smaller than a pinhead, we can track viruses as they interact with living cells, and we can glean the detailed information required to look at pathogens and then design better therapies against them. At the same time, out in the field, we can have DNA sequencers that can aid gene sequencing and help speed up the process of designing new synthetic vaccines with the added advantage of not having to send deadly virus samples around the world.'

The research capabilities of scientists working on the next generation of vaccines and inhibitors to combat viruses and bacterial infections will be greatly enhanced when the UK’s new Electron Bio-Imaging Centre (eBIC) opens in late 2015. Conveniently located next to Diamond’s synchrotron building on the Harwell Science and Innovation Campus in Oxfordshire, the centre’s powerful cryo-electron microscopes will allow scientists to visualise the structure of the cell to help further understand molecular make-up and will provide new tools to image single bio-molecules.

The new centre will offer single particle analysis of biological macromolecules and cellular tomography, as well as electron crystallography. These techniques will complement the atomic mapping possible with the established macromolecular crystallography beamlines. Additional capabilities coming online in the future are elemental mapping in cells provided by the X-ray nanoprobe and the larger scale cell imaging capability of the new Full Field Cryo Transmission X-ray Microscope (cryo-TXM).

These complementary new facilities are expected to draw scientists from around the world, and establish the nation’s synchrotron as a hub of world-leading research into disease prevention.

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