Bovine respiratory syncytial virus

Respiratory disease in young calves is a major animal welfare problem, affecting approximately 1.9 million calves in the UK each year, at a cost of £54 million. BRSV is the most important primary viral cause of respiratory disease in young calves in the UK. This virus is structurally and antigenically related to human (H)RSV, which is the single most important cause of bronchiolitis and pneumonia in infants. The high degree of similarity between HRSV and BRSV indicates that comparative studies of the immunobiology of these viruses will yield important insights that should benefit both man and cattle. Furthermore, BRSV has provided an ideal model to study the function of bovine class I major histocompatability complex (MHC) molecules, virus-specific bovine T cells, and to investigate antigen-delivery systems for induction of specific types of immune response. This work underpins studies on many of the major livestock pathogens that we study in the Institute.

The development of safe and effective RSV vaccines has been hampered by the need to induce protective immunity within the first month of life, at a time when maternal antibodies can pose a major obstacle to successful vaccination; and the observation that vaccination can exacerbate RSV disease. Because vaccine-augmented disease is associated with inactivated virus, it has been proposed that a live, attenuated virus administered intranasally would make a safer and more effective vaccine. The lack of disease potentiation following natural RSV infection is a critical safety advantage of the live vaccine strategy. The mucosal route of vaccination would directly stimulate local immunity, prime CD8+ T cells, which are important in virus clearance, and overcome the immunosuppressive effects of maternally-derived antibodies. Recent advances in the molecular biology of negative-sense RNA viruses have provided a means to manipulate the genome of BRSV and opened the way for producing genetically stable, attenuated BRSV vaccine candidates.

Our research on BRSV includes the following:

  • Analysis of the molecular determinants of virulence of BRSV in order to identify suitable attenuated virus vaccine candidates
  • Characterisation of BRSV-specific CD8+ T cells in order to determine if qualitative or quantitative differences in their priming influences the outcome of infection
  • Investigation of the ways in which the immune response to RSV can be manipulated in order to induce protective immunity whilst avoiding potentially damaging immune responses
  • Identification of immune inductor and effector sites in the upper airways of cattle
  • Analysis of the influence of the site of antigen expression on induction of mucosal immunity

Publications:

  • K. Goris, S. Uhlenbruck, C. Schwegmann-Wessels, W. Köhl, F. Niedorf, M. Stern, M. Hewicker-Trautwein, R. Bals, G. Taylor, A. Braun, G. Bicker, M. Kietzmann & G. Herrler (2009) Differential sensitivity of differentiated epithelial cells to respiratory viruses reveals different viral strategies of host infection. Journal of Virology. 83:1962-1968. [Abstract].
  • R. Lizundia, K.S. Sauter, G. Taylor & D. Werling (2008) Host species-specific usage of the TLR4-LPS receptor complex. Innate Immunity.14:223-231.
  • Valarcher J-F & Taylor G (2007) Bovine respiratory syncytial virus. Vet. Res. 38:153-180.
  • Valarcher J-F, Furze J, Wyld SG, Cook R, Zimmer G, Herrler G & Taylor (2006) Bovine respiratory syncytial virus (BRSV) lacking the virokinin or with a mutation in furin cleavage site RA(R/K)R109 induces less pulmonary inflammation without impeding the induction of protective immunity in calves. J. Gen. Virol. 87:1659-1667. [Abstract].
  • Taylor G, Bruce C, Barbet AF, Wyld SG & Thomas LH (2005) DNA vaccination against respiratory syncytial virus in young calves. Vaccine, 23:1242-1250. [Abstract].
  • Valarcher J-F, Furze J, Wyld S, Cook R, Conzelmann K-K & Taylor G (2003) Role of alpha/beta interferons in the attenuation and immunogenicity of recombinant bovine respiratory syncytial viruses lacking NS proteins. Journal of Virology, 77:8426-8439. [Abstract].
  • Gaddum RM, Cook RS, Furze JM, Ellis SA & Taylor G (2003) Recognition of bovine respiratory syncytial virus proteins by bovine CD8+ T lymphocytes. Immunology: 108:220-229. [Abstract].
  • Bembridge GP, Rodriguez N, Garcia-Beato R, Nicolson C, Melero JA & Taylor G (2001) Respiratory syncytial virus infection of gene gun vaccinated mice induces Th-2 driven pulmonary eosinophilia even in the absence of sensitisation to the fusion (F) or attachment (G) protein. Vaccine, 19:1038-1046. [Abstract].