Abstract
Bluetongue (BT) is an economically important infectious disease of sheep, cattle, goats and deer caused by bluetongue virus (BTV), which is spread by types of biting midges. Animals infected with BTV develop fever, reddening and swelling of the lips, mouth, nasal passages and eyelids, lose condition rapidly, develop muscle degeneration and lameness and may die from the disease. There are at least 24 different types of BTV and, until recently, the disease was largely confined to regions within Africa, Asia, the Americas and Australia. However, as a result of climate change and warmer weather in Europe, BTV-infected midges spread into southern Europe and in 2006 an outbreak of bluetongue occurred in some northern European countries. This was the first time that BTV has been known in northern Europe and in August 2007, the virus spread to the UK. During late 2007/early 2008 BTV serotype 1 arrived in southern France and its distribution overlaps with BTV-8. This raises the possibility that these strains of virus will exchange genes. This may enhance the ability of BTV-1 mixed progeny strains to spread northwards and increase the threat of a second serotype (BTV-1) in northern Europe and the UK. During 2008, a third strain of virus, BTV-6, was detected in the Netherlands and Germany. Control measures in recently infected countries include restrictions on animal movement, which have a significant economic impact, and vaccination. The aims of BTV vaccination are to prevent clinical disease; prevent new animals becoming infected and to allow the safe movement of animals from infected areas. Voluntary vaccination with an inactivated BTV-8 vaccine was introduced into the UK in 2008. Both disabled (modified live) and killed BTV vaccines have been used, but they both have a number of shortcomings. The main problem is that immunity induced by one serotype of BTV only protects against infection with the same serotype. Modified live virus vaccines, which are cheap to produce and generate protective immunity after a single dose, can induce clinical disease in certain susceptible breeds of sheep and have the potential to be spread by midges with the possibility of changing back to a virus that can cause severe disease. Although killed vaccines are safe if properly produced, it is difficult to determine whether animals have been infected or vaccinated; production costs are high and there are marked differences in the response of different breeds of animals to vaccination. Since the current inactivated BTV-8 vaccines are entirely BTV serotype specific, a new vaccine would need to be developed to protect against the potential threat to the UK of BTV-1 and BTV-6, increasing the cost of laboratory diagnosis and distribution of the vaccines. Induction of immune responses that protect against a number of different BTV serotypes could play a significant part in the development of a more widely cross-protective BTV vaccine. Whereas antibody to BTV tends to be serotype-specific, there is evidence that cell-mediated immunity (T cells) is more cross-reactive. However, the role of T cells in protection against BTV is not clear. In this project, we will investigate the role of cell-mediated immunity in recovery from BTV infection in cattle. The findings from these studies will identify elements of the immune response that are responsible for protection and this information will facilitate the development of novel BT vaccine strategies.
Technical Summary
Bluetongue virus (BTV) causes a non-contagious, infectious, arthropod-borne acute haemorrhagic fever of domesticated and wild ruminants. There are at least 24 serotypes of BTV, and neutralising antibodies, which can mediate protection, are largely serotype-specific. As a result of climate change, BTV appeared in northern Europe for the first time during 2006, with devastating effects on the sheep and cattle industry. The virus, BTV-8, spread to the UK in 2007, and in 2008, BTV-1 appeared in southern France and BTV-6 in the Netherlands and Germany, representing an additional threat to the UK. Vaccination plays an important part in the control of BT. However, current inactivated BTV vaccines are relatively crude and are serotype-specific. New and improved vaccines need to be developed to control the threat posed by BTV-8 and incursions by other serotypes. The development of a vaccine that induces a cross-serotype immune response could play a significant part in development of more effective vaccination strategies. There is evidence that some T-cell responses are cross-reactive and play a role in protection in sheep. However, the T cell subsets that mediate protection are not clearly understood. The aim of this project is to determine the role of different T-cell subsets in the resolution of BTV infection in cattle. This will be achieved by depleting cattle of individual T-cell subsets using monoclonal antibodies. This project will identify components of the T-cell response that are important in controlling BTV and will provide the basis for future studies to determine the cross-reactivity and antigenic specificity of the protective T cells. This informaiton will aid the development of novel more widely cross-reactive, BT vaccine strategies.