Dr Bryan Charleston
	Tel:	+44 (0)1483 231 010 or +44 (0)1635 577 300
	E-mail:	bryan.charleston@bbsrc.ac.uk
	Address:	Institute of Animal Healt, Pirbright Laboratory Pirbright, Surrey GU24 0NF
	Website:	www.iah.ac.uk/research/immexovirinf/immexovirinf.shtml

Principal areas of research
Foot-and-Mouth Disease virus, dendritic cells, bovine immunology.

Biography
Dr Charleston obtained a BVetMed from the Royal Veterinary College, University of London, UK in 1982. After a period of time in Large Animal Practice, studied for a Masters degree in Molecular Biology at University College London in 1988, then a PhD degree, as a Wellcome Trust Scholar, from the University of London, UK, in 1991. He then carried out postdoctoral research, as a Wellcome Trust Post-doctoral fellow, at the Royal Veterinary College and the Babraham Institute, Cambridge for three years. He joined the Institute for Animal Health in 1994 and focussed on studies of the immune response to viral infections in cattle. In addition, he has provided advice and expertise on the design of infectious disease challenge models for a wide range of pathogens in important agricultural species. His research groups are based at the Compton site near Oxford and the Pirbright site in Surrey; the group’s efforts are focused on understanding the immune response to Foot-and–Mouth disease virus in cattle to develop novel vaccines.

Research
Foot and mouth disease virus (FMDV) causes an acute vesicular disease in cattle sheep and pigs, which results in debilitation, pain and loss of productivity. Because of the highly contagious nature of the disease, infection spreads rapidly through susceptible populations of animals and can give rise to severe epidemics.

The Global FMD Research Alliance (GFRA) was launched as an international consortium of five institutions (Pirbright Laboratories, (UK), Plum Island Laboratories, (USA), National Centre for Foreign Animal Disease (Canada), Australian Animal Health Laboratory and the International Livestock Research Institute, Kenya), with a five year research program for developing a new generation of vaccines and other technologies for the control of FMD.

The central core of the GFRA is to establish an alliance between the four high security laboratories, to foster synergism on the current FMD research activities and current gaps to address the needs of their host nations, drawing on public sector funding by individual governments. GFRA will focus on the delivery of a series of products to better manage the incursion of FMD into free areas. Taking advantage of this alliance of global expertise on FMD research, the GFRA will develop a separate program, for the wider control of FMD in endemic areas, bringing to bear the knowledge, expertise and leverage offered by the Alliance partners.

The contribution of the UK laboratory at the Institute for Animal Health in Pirbright will be to develop a vaccination strategy that induces a rapid induction of protective antibody and cell mediated immune responses. Work funded by the BBSRC (Biotechnology and Biological Sciences Research Council) at IAH to develop immunological correlates of protection against FMDV has indicated how currently available vaccines could be improved. Protection against FMDV has been related to the quantity of serum antibody, however, we have shown protection also depends on the magnitude of the cell mediated response.

Improving vaccine performance will be addressed by two related strategies: firstly, developing vaccines to specifically drive cell mediated immune responses to be used in conjunction with current vaccines; secondly, developing methods to produce stable FMDV capsids on an industrial scale. Analysis of the immune response to a number of different viruses suggests stable capsids are highly effective at driving antibody and cell mediated immune responses, we have evidence to suggest this is also the case for FMDV. In addition to the intrinsic ability of the stable capsid structures to stimulate protective immune responses, they will provide an opportunity to increase antigen payload to improve vaccine efficacy. An added benefit of producing viral capsids is their use in improving diagnostic test.

Key Publications
Lefevre EA, Hein WR, Stamataki Z, Brackenbury LS, Supple EA, Hunt LG, Monaghan P, Borhis G, Richard Y, Charleston B.
Fibrinogen is localized on dark zone follicular dendritic cells in vivo and enhances the proliferation and survival of a centroblastic cell line in vitro.
J Leukoc Biol. 2007 Sept. Epub

Gerner W, Carr BV, Wiesmuller KH, Pfaff E, Saalmuller A, Charleston B
Identification of a novel foot-and-mouth disease virus specific T-cell epitope with immunodominant characteristics in cattle with MHC serotype A31.
Vet Res. 2007 38, 565-572.

Meyers G, Ege A, Fetzer C, von Freyburg M, Elbers K, Carr V, Prentice H, Charleston B, Schurmann EM.
Bovine viral diarrhoea virus: Prevention of persistent foetal infection by a combination of two mutations affecting the Erns RNase and the Npro protease.
J. Virol. 2007 81, 3327-38.

Hope JC, Howard CJ, Prentice H, Charleston B
Isolation and purification of afferent lymph dendritic cells that drain the skin of cattle.
Nature Protocols 2006 1, 982-987

Brackenbury LS, Carr BV, Stamataki Z, Prentice H, Lefevre EA, Howard CJ, Charleston B
Identification of a cell population that produces alpha/beta interferon in vitro and in vivo in response to noncytopathic bovine viral diarrhea virus.
J Virol. 2005 79, 7738-44

Glew EJ, Carr BV, Brackenbury LS, Hope JC, Charleston B, Howard CJ.
Differential effects of bovine viral diarrhoea virus on monocytes and dendritic cells.
J Gen Virol. 2003 84, 1771-80.

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