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UK funding (£551,435): Reverse genetics to map determinants of Varicella zoster Oka vaccine attenuation and virulence. Ukri1 Jun 2008 UK Research and Innovation, United Kingdom
Overview
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Reverse genetics to map determinants of Varicella zoster Oka vaccine attenuation and virulence.
| Abstract | Chickenpox is a common infection of childhood which is usually uncomplicated. Following infection, the causative virus, known as varicella-zoster virus (VZV) remains dormant within the nerves reactivating at a later date in some people to cause shingles. In adults and in people with depressed immunity (HIV+ve, transplant patients, underlying congenital immunodeficiency, or receiving immunosuppressive drugs) chickenpox is more commonly fatal. A vaccine, called vOka, is licensed for the prevention of chickenpox and shingles and is widely used in the USA, parts of Europe and Canada. Although extremely safe it causes a rash in about 5% of healthy vaccinees. Unfortunately the vaccine can also cause life threatening disease in those who are already most at risk of ordinary chickenpox, namely immunosuppressed patients. Since these are the patients would be likely to benefit most from immunisation, a safer vaccine is urgently required. Previous work has identified that the vOka vaccine contains mixture of closely related variant viruses. We have shown that only a few of the variants within the vaccine preparation are responsible for causing vaccine rashes. These rash-forming vaccine variants are more likely to carry certain mutations within one gene known as ORF62. At the same time, we have access to an experimental batch of the Oka vaccine which was never licensed because it caused too many rashes. Finally, we have identified a case in which the vaccine virus appeared to become virulent, transmitting from a child with a rash to his parent who developed a full blown case of chickenpox. We now propose to look at the genetic sequences of these rash-causing viruses and compare them with the vaccine itself and the original virus from which the vaccine was made. We will examine whether these more virulent vaccine viruses behave differently in models of skin and develop new methods to assess whether certain proteins within the virus including the protein coded for by ORF62 are altered in the vaccine and in the rash-causing vaccine viruses. Importantly, the results will provide information which will help in the development of new, improved vaccines to prevent chickenpox and shingles. |
| Category | Research Grant |
| Reference | G0700814/1 |
| Status | Closed |
| Funded period start | 01/06/2008 |
| Funded period end | 31/07/2009 |
| Funded value | £551,435.00 |
| Source | https://gtr.ukri.org/projects?ref=G0700814%2F1 |
Participating Organisations
| Queen Mary University of London |
The filing refers to a past date, and does not necessarily reflect the current state. The current state is available on the following page: Queen Mary University of London, London.
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