Despite the success of vaccines produced from "virus-like particles" (VLPs) for hepatitis B and human papilloma viruses, poliovirus VLPs have proved to be too unstable to make practical vaccines.
Now, a research team from the Faculty of Biological Sciences (FBS) has found a new way to modify these VLPs, also known as "empty capsids", by identifying mutations which make their structures sufficiently stable to act as vaccines.
The empty capsids change shape when warmed and become unusable as vaccines, but the mutations identified in this research prevent these damaging changes.
Polio is on the verge of being eradicated world-wide, but even when it has been officially declared as extinct as a disease, governments will need to continue to vaccinate to ensure it does not recur.
Using current technology, the production of vaccine requires the growth of enormous quantities of live virus, which is then chemically killed, thus presenting a dangerous security risk of virus escaping into the environment.
These stabilised VLPs are suitable as replacements for the killed poliovirus vaccines and can be produced in ways that do not require the growth of live virus.
The Leeds team and collaborators say this form of vaccine, using the newly developed stabilised VLPs, would be best used after the virus has been eradicated.
David Rowlands, Professor of Molecular Virology and co-leader of the study at the University, said: “Continuing to vaccinate after polio has been eradicated is essential to ensure against the disease recurring, but there are significant biosafety concerns about current production methods.
“Our new method of creating the vaccine has been proven to work in lab conditions and on top of that we’ve proved it’s actually more stable than existing vaccines.
“The improved stability of these modified VLPs means that they can be produced using bioengineering techniques without involving the growth of live virus.”
Professor Nicola Stonehouse, co-leader of the study, from FBS, said: “The international drive to eradicate polio using existing vaccines continues, but methods need to be found to maintain vaccination safely as insurance after it appears to have been eradicated. This is when our approach will come into its own.
“Further research is needed to refine them more but we are confident they will work for all three forms of polio. After that we need to find a way to manufacture them cost effectively on a large scale.”
The research has been funded through a $1.5 million World Health Organisation grant to a consortium led by Leeds and including the National Institute for Biological Standards and Control (NIBSC), John Innes Centre (JIC) in Norwich, the University of Oxford, University of Reading, and the Pirbright Institute.
The image above is an electron micrograph of live poliovirus particles (left) and empty particles (potential VLP vaccine) (right). The VLPs contain no infectious viral RNA and so the stain used fills the empty space making them appear black.
The results come in the same month as other members of the Leeds-led consortium (NIBSC) also published a related paper in the PloS Pathogens journal describing a slightly different approach to the development of stable polio VLP vaccines.
Professors Rowlands and Stonehouse are available for media interviews, and the featured image is also available. Please contact Peter Le Riche in the University press office on 0113 343 2049 or email email@example.com
Ralf Richter, David Brockwell, Eric Hewitt, Jessica Kwok, Emanuele Paci and MAPS/FMH, BBSRC (Jun 2017), £600,000
Eric Blair, Adrian Whitehouse, Nicola Stonehouse, Alison Baker, Richard Bayliss, Joan Boyes, Ryan Seipke, Sally Boxall and MAPS/FMH, BBSRC (Jun 2017), £376,000
Stefan Kepinski, Yoselin Benitez-Alfonso, Tom Bennett, Michelle Peckham, BBSRC (Jun 2017), £331,000
Roman Tuma, Lars Jeuken, Paul Millner, Sheena Radford, Peter Stockley and MAPS/FMH, BBSRC (Jun 2017), £222,000
Vas Ponnambalam, Darren Tomlinson, Stephen Wheatcroft, BHF (May 2017), £107,878
Graham Askew in collaboration with Bangor University, BBSRC (Mar 2017), £477,383
Stephen Muench, BBSRC (Mar 2017), £132,945
Nic Stonehouse, MRC (Mar 2017), £906,341
Bill Kunin, Steve Sait, BBSRC (Mar 2017), £602,831
Adrian Goldman, EU (Mar 2017), £546,576
Sheena Radford, Wellcome Trust (Mar 2017), £1,836,482
Beatrice Filippi, Royal Society (Mar 2017), £15,000
Jamie Johnston, Royal Society (Mar 2017), £15,000
Tom Bennett, Royal Society (Mar 2017), £15,000
Ryan Seipke, BBSRC (Feb 2017), £52,116
Mary O'Connell, BBSRC (Feb 2017), £46,986
Hannah Dugdale, NERC (Feb 2017), £504,138
Anastasia Zhuravleva, EPSRC (Jan 2017), £100,792
Richard Bayliss, Cancer Research UK (Jan 2017), £1,600,000
John Barr, EU (Jan 2017), £339,000
Mark Harris, Royal Society (Jan 2017), £250,000
Alison Dunn, NERC (Jan 2017), £105,000
Alex Breeze, Pancreatic Cancer Research Fund (Jan 2017), £180,000
Alison Dunn, NERC (Dec 2016), £18,000
Lisa Collins, BBSRC (Dec 2016), £1,681,835
Brendan Davies, Leverhulme Trust (Dec 2016), £247,555
Alan Benson, Mark Drinkhill, Ed White, British Heart Foundaion (Dec 2016), £217,223
Adrian Goldman, Royal Society (Dec 2016), £82,999
Lisa Roberts, Alex Breeze, Brendan Davies, Timothy Devinney, Oliver Harlen, Joseph Holden, Anthea Hucklesby, Pamela Jones, Philip Mellor, RCUK (Nov 2016), £484,172
Lisa Roberts, Alex Breeze, Brendan Davies, Timothy Devinney, Oliver Harlen, Joseph Holden, Anthea Hucklesby, Pamela Jones, Philip Mellor, Wellcome Trust (Nov 2016), £119,343
Katie Field, Rank Prize Funds (Nov 2016), £20,000
Jessica Kwok, Royal Society (Nov 2016), £14,948
John Ladbury, Cancer Research UK (Oct 2016), £4,250
Miriam Wittmann, Martin Stacey, Edward Vital, Lupus UK
(Oct 2016), £34,010
Valerie Speirs, NC3Rs
(Oct 2016), £90,000
Nicola Stonehouse, Morgan Herod, David Rowlands, BBSRC
(Sep 2016), £436,424
Joseph Cockburn, Wellcome Trust
(Sep 2016), £100,000
John Barr, Public Health England
(Sep 2016), £94,471
Helen Miller, DSM Nutritional Products A/S
(Sep 2016), £54,680
Steven Clapcote, Vitaflo International Ltd
(Sep 2016), £39,285
Juan Fontana Jordan De Urries
, Royal Society
(Sep 2016), £21,793
Jing Li, Sarah Calaghan, Mark Drinkhill, British Heart Foundation
(Sep 2016), £117,585
Sheena Radford, Alison Ashcroft, BBSRC (Sep 2016), £457,216
Patricija Van Oosten-Hawle, An-Jung Chen, David Westhead, NC3Rs
(Sep 2016), £354,456
Glyn Hemsworth, BBSRC (Sep 2016), £1,024,034