Publications

Bluetongue (BT) is a disease of ruminants caused by bluetongue virus (BTV), which is spread between its hosts by Culicoides midges. Vaccination is the most effective way to protect susceptible animals against BTV and was used reactively to control the recent northern European outbreak. To assess the consequences of using vaccination pre-emptively we used a stochastic, spatially explicit model to compare reactive and pre-emptive vaccination strategies against an incursion of BTV serotype 1 (BTV-1) into Great Britain. Both pre-emptive and reactive vaccination significantly reduced the number of affected farms and limited host morbidity and mortality. In addition, vaccinating prior to the introduction of disease reduced the probability of an outbreak occurring. Of the strategies simulated, widespread reactive vaccination resulted in the lowest levels of morbidity. The predicted effects of vaccination were found to be sensitive to vaccine efficacy but not to the choice of transmission kernel.

African swine fever virus (ASFV) infection usually results in an acute haemorrhagic disease with a mortality rate approaching 100% in domestic pigs. However, pigs can survive infection with less-virulent isolates of ASFV and may become chronically infected. Surviving animals are resistant to challenge with homologous or, in some cases, closely related isolates of the virus indicating that pigs can develop protective immunity against ASFV. During asymptomatic, non-virulent ASFV infections natural killer cell activity increases in pigs, suggesting this cell type plays a role in ASFV immunity. Furthermore, depletion of CD8+ lymphocytes from ASFV immune pigs demolishes protective immunity against related virulent viruses. This suggests that ASFV specific antibody alone is not sufficient for protection against ASFV infection and that there is an important role for the CD8+ lymphocyte subset in ASFV protective immunity. These results were supported by DNA immunization studies, demonstrating a correlation between the protection afforded against lethal challenge and the detection of a large number of vaccine-induced antigen-specific CD8+ T-cells. Peripheral blood mononuclear cells (PBMCs) from ASF immune pigs protected from clinical disease show higher proportions of ASFV specific CD4+CD8high+ double positive cytotoxic T cells than PBMCs from ASF immune but clinically diseased pig. The frequency of ASFV specific IFN? producing T cells induced by immunization correlates to the degree of protection from ASFV challenge, and this may prove to be a useful indicator of any potential cross-protection against heterologous ASFV isolates.

Bovine respiratory syncytial virus (BRSV), which is an important cause of respiratory disease in young calves, is genetically and antigenically closely related to human (H)RSV. The epidemiology and pathogenesis of infection with these viruses are similar. The viruses are host-specific and infection produces a spectrum of disease ranging from subclinical to severe bronchiolitis and pneumonia, with the peak incidence of severe disease in individuals less than 6 months of age. BRSV infection in calves reproduces many of the clinical signs associated with HRSV in infants, including fever, rhinorrhoea, coughing, harsh breath sounds and rapid breathing. Although BRSV vaccines have been commercially available for decades, there is a need for greater efficacy. The development of effective BRSV and HRSV vaccines face similar challenges, such as the need to vaccinate at an early age in the presence of maternal antibodies, the failure of natural infection to prevent reinfection, and a history of vaccine-augmented disease. Neutralising monoclonal antibodies (mAbs) to the fusion (F) protein of HRSV, which can protect infants from severe HRSV disease, recognise the F protein of BRSV, and vice versa. Furthermore, bovine and human CD8+ T-cells, which are known to be important in recovery from RSV infection, recognise similar proteins that are conserved between HRSV and BRSV. Therefore, not only can the bovine model of RSV be used to evaluate vaccine concepts, it can also be used as part of the preclinical assessment of certain HRSV candidate vaccines.

Although CD1d and NKT cells have been proposed to have highly conserved functions in mammals, data on functions of CD1d and NKT cells in species other than humans and rodents are lacking. Upon stimulation with the CD1d-presented synthetic antigen alpha-galactosylceramide, human and rodent type I invariant NKT cells release large amounts of cytokines. The two bovine CD1D (boCD1D) genes have structural features that suggest that they cannot be translated into functional proteins expressed on the cell surface. Here we provide evidence that despite an intron-exon structure and signal peptide that are different from all other known CD1 genes, boCD1D can be translated into a protein that is expressed on the cell surface. However, in vivo treatment of cattle (Bos taurus) with 0.1, 1, or 10 mu g kg(-1) of the most commonly used a-galactosylceramide, which has a C26 fatty acid, did not lead to an increase in body temperature and serum cytokine levels of the animals. This lack of reactivity is not due to a complete inability of boCD1d to present glycosphingolipids because a-galactosylceramide variants with shorter fatty acids could be presented by boCD1d to human NKT cells in vitro. This suggests that the natural ligands of boCD1d are smaller lipids.