New method makes vaccines stable at tropical temperatures

New method makes vaccines stable at tropical temperatures
18 February 2010


A simple and cheap way of making vaccines stable - even at tropical temperatures - has been demonstrated by scientists at Oxford University and Nova Bio-Pharma Technologies.

The British technology has the potential to revolutionise vaccination efforts, particularly in the developing world where infectious diseases kill millions of people every year, by removing the need for fridges, freezers and associated health infrastructure.

The work, funded by the Grand Challenges in Global Health partnership with other funds from the Wellcome Trust, is published in the journal Science Translational Medicine.

Preparing vaccines that do not need refrigeration has been identified as one of the major unsolved problems in global health.

‘Currently vaccines need to be stored in a fridge or freezer,' explains lead author Dr Matt Cottingham of the Jenner Institute at the University of Oxford. ‘That means you need a clinic with a nurse, a fridge and an electricity supply, and refrigeration lorries for distribution.

‘If you could ship vaccines at normal temperatures, you would greatly reduce cost and hugely improve access to vaccines,' he says. ‘You could even picture someone with a backpack taking vaccine doses on a bike into remote villages.'

Oxford University carried out the proof-of-concept study, showing that vaccines they are developing could be stabilised for months using Nova's patented Hypodermic Rehydration Injection System (HydRIS).

The team demonstrated it was possible to store two different virus-based vaccines on sugar-stabilised membranes for 4-6 months at 45°C without any degradation. The vaccines could be kept for a year and more at 37°C with only tiny losses in the amount of viral vaccine re-obtained from the membrane.

‘We've shown that a very simple way of heat-stabilising vaccines works for two viruses that are being used as the basis for novel vaccines in development,' says principal investigator Professor Adrian Hill of Oxford University. ‘This is so exciting scientifically because these viruses are fragile. If we are able to stabilise these, other vaccines are likely to be easier.'

The method involves mixing the vaccine with the sugars trehalose and sucrose. The mixture is then left to slowly dry out on a simple filter or membrane. As it dries and the water evaporates the vaccine mixture turns into a syrup and then fully solidifies on the membrane.

The thin sugary film that forms on the membrane preserves the active part of the vaccine in a kind of suspended animation, protected from degradation even at high temperature. Flushing the membrane with water rehydrates the vaccine from the membrane in an instant.

‘The beauty of this approach is that a simple plastic cartridge, containing the membrane with vaccine dried on, can be placed on the end of a syringe,' explains Dr Cottingham. ‘Pushing a liquid solution from the syringe over the membrane would then release the vaccine and inject it into the patient.'

The process is general and could be used for many types of vaccines and sensitive biological agents.

Professor Hill adds: ‘The World Health Organisation's immunisation program vaccinates nearly 80% of the children born today against six killer diseases: polio, diphtheria, tuberculosis, whooping cough, measles and tetanus. One of the biggest costs is maintaining what's called the cold chain - making sure vaccines are refrigerated all the way from the manufacturer to the child, whether they are in the Western world or the remotest village in Africa. If most or all of the vaccines could be stabilised at high temperatures, it would not only remove cost, more children would be vaccinated.'

Dr Peter White, Nova's managing director, said the work by Oxford University demonstrated one successful application of Nova's patented HydRIS technology platform and that Nova has already successfully stabilised a wide range of viral and conventional vaccines.

‘This new technique of drug delivery is one of the most exciting developments in the British pharmaceutical and biotechnology industries, especially as it can be used for highly unstable products, for instance vaccines for malaria.'

For more information please contact the Press Office, University of Oxford on +44 (0)1865 280530 or [email protected]


Notes to Editors
 Preparing vaccines that do not require refrigeration is one of the grand challenges identified by the Grand Challenges in Global Health, a partnership launched by the Bill and Melinda Gates Foundation http://www.grandchallenges.org/ImproveVaccines/Challenges/HeatStable/Pages/default.aspx
Current childhood vaccines require refrigeration to maintain stability and viability. Transportation, storage, and delivery up to the point of use require an intact cold chain, which is difficult and exceedingly costly to maintain. Successful development of heat-stable vaccine products will simplify vaccine storage and delivery, reduce waste, and improve vaccine efficacy.
In the developed world, maintaining the cold chain is estimated to cost up to $200 million a year and increases the cost of vaccination by 14-20% (source World Health Organisation). In the developing world, that infrastructure can be missing or incomplete and presents a great barrier to effective vaccination schemes.
The paper ‘Long-term thermostabilisation of live poxviral and adenoviral vaccine vectors at supraphysiological temperatures in carbohydrate glass' by Robert Alcock and colleagues will be published online in the journal Science Translational Medicine.
The scientists used viruses that are being used as the basis for some of the latest vaccines in development. These are live viruses that have been engineered so that they can enter a cell in the body and stimulate an effective immune response, but they cannot replicate and so cannot cause an infection. It is crucial for this new type of live-virus-based vaccine that the viruses remain alive over long shelf-lives, which this method is able to achieve. The team at Oxford University has pioneered the use of these viruses as the basis for developing promising new vaccines against TB, malaria, HIV/AIDS and flu, all of which are currently in clinical trials.
 Isis Innovation, Oxford University's technology transfer company, is working with the inventors to put a commercial strategy in place for the development of the technology.
The next steps are to show the process can be scaled up to industrial manufacturing levels and demonstrate it works with a standard or newly licensed human vaccine.
The research was funded by a grant from the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative, with other support from the Wellcome Trust.
Nova Laboratories has developed a worldwide reputation for consistently being at the forefront of technological exploration and clinical standards. The company has MHRA-approved, state-of-the-art facilities at Wigston in Leicester, where it has developed world class expertise in aseptic processing of complex pharmaceuticals, using sterile isolation technology.
Nova was established - and is still owned - by ex-NHS professionals following a management buy-out in 1994. The majority of the original NHS team are still with the company, which now has 140 highly-qualified employees.
The Foundation for NIH was established by the United States Congress to support the mission of the National Institutes of Health - improving health through scientific discovery in the search for cures. It expedites or facilitates new discoveries by convening innovative public/private collaborative partnerships that leverage the diverse strengths of stakeholders including those from the scientific and research community, industry, academia, advocacy groups, foundations and philanthropy. The foundation is a non-profit, 501(c)(3) corporation, that raises private-sector funds for a broad portfolio of programs that complement and enhance NIH priorities and activities.http://www.fnih.org.
The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending over £600 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing. http://www.wellcome.ac.uk
The research was conducted primarily at the Jenner Institute laboratories of the University of Oxford. The Jenner Institute was established by the Jenner Vaccine Foundation - a UK charity that secures resources to facilitate the development of new vaccines against human and veterinary diseases of global impact.
Isis Innovation is the University of Oxford's technology transfer company and manages the University's intellectual property portfolio, working with University researchers on identifying, protecting and marketing technologies through licensing, spin-out company formation and material sales. Isis files on average one new patent application each week, has concluded over 400 technology licensing agreements, and established 64 new spin-out companies from Oxford. Isis also manages Oxford University Consulting, which arranges consulting services providing clients access to the world-class expertise of the University's academics to enhance innovative capability. Last year OUC arranged over 150 consulting deals. Isis has established a separate business division, Isis Enterprise, offering consulting expertise and advice in technology transfer and open innovation to university, government and industrial clients around the world. Isis was founded in 1987 and is today one of the world's leading technology transfer and innovation management companies. www.isis-innovation.com
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.

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