The project has been awarded $500,000 from the Bill and Melinda Gates Foundation, through the World Health Organisation, and aims to be effective against all polio subtypes.
Led by Professor Dave Rowlands and Dr Nicola Stonehouse from the University’s Faculty of Biological Sciences, the research team will design a replica virus particle that looks and behaves like the real virus, but is actually an empty protein shell.
The researchers believe the hoax virus will trigger the body’s immune system, but because it does not contain the genetic blueprint that replicates the virus inside the body, has no chance of causing or helping to spread the disease.
“This is an entirely new strategic approach against polio,” says Dr Stonehouse. “This project is not about improving the efficiency of the current types of vaccine. Our intention is to design and produce a replica virus particle that carries no RNA cargo. This means it will be entirely safe to use as it can’t ever cause the disease, and unlike current vaccines, can be produced without needing to grow large amounts of the infectious virus.”
The team, led by Leeds, brings together researchers from Harvard University, the University of Oxford and the UK’s National Institute for Biological Standards and Control (NIBSC), a centre of the Health Protection Agency. The first stage of the research will focus on proving that that the new approach is viable against the virus.
Current polio vaccines in use around the world are either delivered orally or injected, but contain either a weakened form of the virus, or an inactivated virus to kickstart the immune response. Whilst these have been extremely successful in reducing polio globally, the virus persists in several countries and unexpected outbreaks still occur.
“What excites me about this project is that we’re working towards a risk-free vaccine that will be essential for the complete eradication of polio from the globe,” adds Dr Stonehouse. “As well as being safe to produce and use, it will be stable enough not to need refrigeration and could be injected as part of current childhood vaccination programmes.”
Although a similar approach using replica virus particles has been used successfully to create the human papilloma virus (HPV) vaccine against cervical cancer, the complexity of the polio virus creates significant additional challenges.
“With polio, the virus particle’s surface matures and changes because of the genetic material inside, and so ensuring that our replica particle mimics this surface exactly is not going to be easy. Since it’s essentially an empty protein shell, it also has to be robust enough that it doesn’t fall apart,” explains Professor Rowlands. “This will be an iterative process, where we keep testing, refining and improving the particles we design until we achieve exactly the right structure and surface.”
“We believe that if the project is successful, this new approach could help to completely eradicate this disease for good.”
Image: Structure of polio virus as determined by X ray crystallography
Credit: James Hogle, Harvard University
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Fifteen countries have reported confirmed cases of polio in 2010. In four of these: Pakistan, Afghanistan, Nigeria and India, polio is considered to be endemic. (source: World Health Organisation www.polioeradication.org).
Information on current polio vaccines
Oral polio vaccine (OPV) contains a live, but weakened, mutation of the polio virus – strong enough to trigger immunity but weak enough not to cause the disease – and requires only a single dose to be effective. However, the live virus can rapidly revert and become pathogenic again, presenting a risk to non-immune contacts such as family members. In addition, rare individuals carry persistent polio virus, which will provide a dangerous source of virus that could result in future epidemics of polio if childhood vaccination was stopped.
Injected polio vaccine (IPV) contains a wildtype virus that has been inactivated, so is safer to use. However, three separate injections are needed for it to be fully effective and the vaccine has to be transported and stored in temperature-controlled conditions, so it is not ideal to use in regions where political strife or poverty can interfere with vaccination efforts. There is a general consensus of opinion that stopping vaccination will be too dangerous for the foreseeable future and that control in the future will depend entirely on IPV. IPV requires the initial production of a great deal of live virus, which itself poses a potential risk. Therefore, an alternative vaccine produced without the need to grow virus will be very attractive.
The Faculty of Biological Sciences at the University of Leeds is one of the largest in the UK, with over 150 academic staff and over 400 postdoctoral fellows and postgraduate students. The Faculty is ranked 4th in the UK (Nature Journal, 457 (2009) doi :10.1038/457013a) based on results of the 2008 Research Assessment Exercise (RAE). The RAE feedback noted that “virtually all outputs were assessed as being recognized internationally, with many (60%) being internationally excellent or world-leading” in quality. The Faculty’s research grant portfolio totals some £60M and funders include charities, research councils, the European Union and industry. www.fbs.leeds.ac.uk
Oxford University’s Medical Sciences Division is one of the largest biomedical research centres in Europe. It represents almost one-third of Oxford University’s income and expenditure, and two-thirds of its external research income. Oxford’s world-renowned global health programme is a leader in the fight against infectious diseases (such as malaria, HIV/AIDS, tuberculosis and avian flu) and other prevalent diseases (such as cancer, stroke, heart disease and diabetes). Key to its success is a long-standing network of dedicated Wellcome Trust-funded research units in Asia (Thailand, Laos and Vietnam) and Kenya, and work at the MRC Unit in The Gambia. Long-term studies of patients around the world are supported by basic science at Oxford and have led to many exciting developments, including potential vaccines for tuberculosis, malaria and HIV, which are in clinical trials.
The Health Protection Agency is an independent UK organization that was set up by the government in 2003 to protect the public from threats to their health from infectious diseases and environmental hazards. It does this by providing advice and information to the general public, to health professionals such as doctors and nurses, and to national and local government. The National Institute for Biological Standards and Control (NIBSC), a centre of the HPA, is the global leader in the field of biological standardization, responsible for developing and producing over 90% of the International Standards in use around the world to assure the quality of biological medicines – www.hpa.org.uk