African swine fever virus

Vaccinology staff are also working toward the development of a safe and effective ASFV vaccine. ASF is a highly contagious fatal acute haemorrhagic viral disease of pigs which causes major economic losses. ASFV is currently endemic in many sub-Saharan African countries and in Madagascar and Sardinia. There is no vaccine available and disease control relies on implementing movement restrictions and slaughter policies which are difficult to achieve in countries lacking a good infrastructure. To date, the use of empirical methods have failed to produce an effective vaccine, partly due to the complexity of the virus, the acute fatal nature of the disease and a poor understanding of the what types of immune response protect against infection. Recent studies have highlighted an important role for CD8+ T cells in immunity induced by a naturally occurring, avirulent isolate of ASFV. Consequently we are working on the development of a vaccine that induces an appropriate CD8+ T-cell response.

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Our current ASFV studies are:

  • Characterisation of the role of various CD8+ T cell subsets in protection
  • Identification of the ASFV proteins recognized by these cells
  • Development of a vaccine that induces strong CD8+ T-cell responses
  • The effect of ASFV on dendritic cell function and antigen presentation
  • The role of components of the innate immune response e.g. g/d T cells, NK cells and Mx protein in ASFV infection

In these studies, we are collaborating with Linda Dixon?s group who is producing mutant ASFV.

Publications:

  • C.L. Netherton, J. Simpson, O. Haller, T.E. Wileman, H.-H. Takamatsu, P. Monaghan & G. Taylor (2009) Inhibition of a large double-stranded DNA virus by MxA protein. Journal of Virology, 83:2310-2320. [Abstract].
  • P.C. Hawes, C.L. Netherton, T. E. Wileman & P. Monaghan (2008) The envelope of intracellular African swine fever virus is composed of a single lipid bilayer. Journal of Virology 82:7905-7912 [Abstract].
  • C. Netherton, K. Moffat, E. Brooks & T. Wileman (2007) A guide to viral inclusions, membrane rearrangements, factories, and viroplasm produced during virus replication. Advances in Virus Research 70:101-82 [Abstract].
  • M.S. Denyer, T.E. Wileman, C.M.A. Stirling, B. Zuber & H.-H. Takamatsu (2006) Perforin expression can define CD8 positive lymphocyte subsets in pigs allowing phenotypic and functional analysis of Natural Killer, Cytotoxic T, Natural Killer T and MHC un-restricted cytotoxic T-cells. Veterinary Immunology and Immunopathology, 110:279-292. [Abstract].
  • J.G. Sambrook, H. Sehra, P. Coggill, S. Humphray, S. Palmer, S. Sims, H.-H. Takamatsu, T.E. Wileman, A.L. Archibald & S. Beck (2006) Identification of a single killer immunoglobulin-like receptor (KIR) gene in the porcine leukocyte receptor complex on chromosome 6q. Immunogenetics. 58:481-486 [Abstract].
  • C.A Oura, M.S. Denyer, H. Takamatsu & R.M. Parkhouse. (2005) In vivo depletion of CD8+ T lymphocytes abrogates protective immunity to African swine fever virus. Journal of General Virology. 86:2445-50 [Abstract].