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Lighting up a new path for novel synthetic Polio vaccine

: Polio: 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.

Scientists from the UK and USA are using technology that helped in the design of a new synthetic vaccine to combat the foot and mouth disease virus (FMDV) to now target the virus that causes polio. The novel vaccine would provide a powerful weapon in the fight to rid the world of polio, and this project is being funded by a £438,000 grant from the World Health Organisation and the Bill & Melinda Gates Foundation.

The synthetic vaccine is currently being engineered in collaboration with Prof Dave Stuart at Diamond Light Source and the University of Oxford, and Prof. Dave Rowlands and Prof Nicola Stonehouse at the University of Leeds. The project is also supported by the work of Prof Ian Jones at the University of Reading, Drs Andy Macadam and Phil Minor at the National Institute for Biological Standardisation and Control (NIBSC), and Prof George Lonossoff at the John Innes Institute.

The team’s hope is 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. 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. Eventually such vaccines could pave the way to completely eliminating the necessity to vaccinate

Speaking at the American Association for the Advancement of Science (AAAS 2015) meeting in San Jose on the 13^th February 2015, Prof Dave Stuart, Life Sciences Director at Diamond Light Source, the UK’s national synchrotron science facility, and Professor of Structural Biology at Oxford University, explains: “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.”

: Artist’s impression of Diamond’s X-ray nanoprobe beamline (I14), Electron Bio-Imaging Centre (eBIC), and Electron microscopy centre for physical sciences.; Copyright: Diamond Light Source

“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. 21^st Century technology will, he believes, play a key role in helping us to dramatically improve our response times when new virus outbreaks occur. He adds, “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.”

Scientists working on the next generation of vaccines and inhibitors to combat viruses and bacterial infections will have their research capabilities greatly enhanced when the UK’s new Electron Bio-Imaging Centre (eBIC) opens in late 2015. Conveniently located next to Diamond’s synchrotron building, 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 the imaging approaches of 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.

Project goals, UK partners and roles

The overall goals are firstly to isolate and/or design mutant forms of poliovirus that make stable empty virus-like particles (VLPs) suitable for vaccine production and secondly to develop methods to produce such VLPs cheaply and efficiently by recombinant expression technology (e.g. in yeast, insect cells, etc.).

University of Leeds - Prof David Rowlands is the PI on the grant and he and his colleague Dr Nicola Stonehouse are selecting and studying more stable forms of poliovirus type 1 and exploring yeast as a potential production system.

University of Oxford - Prof Dave Stuart is dealing with structural aspects of the project including using in silico analytical approaches to design more stable VLPs. He is also investigating VLP production in mammalian cell culture.

University of Reading - Prof Ian Jones is investigating recombinant expression systems (especially in insect cells using baculovirus vectors) for production of VLPs.

National Institute for Biological Standardisation and Control (NIBSC) - Drs Andy Macadam and Phil Minor are constructing more stable mutant forms of poliovirus types 2 and 3. They are in an expert situation to directly compare our VLP vaccines with current commercial vaccines.

John Innes Institute - Prof George Lomonossoff is exploring the potential of using plants to express the VLP particles.

Diamond Light Source is the UK's national synchrotron science facility, located at the Harwell Science and Innovation Campus in Oxfordshire.

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Lighting up a new path for novel synthetic Polio vaccine