Professor Andy Morgan
Professor of Virology
School of Cellular and Molecular Medicine,
University of Bristol, Medical Sciences Building,
Bristol, BS8 1TD
phone: +44 (0)117 33 12069 (internal 12069)
email: andy.morgan@bristol.ac.uk
Research interests
A number of important human cancers are associated with Epstein-Barr virus (EBV) including endemic Burkitt's lymphoma, nasopharyngeal carcinoma, a proportion of gastric carcinomas, certain Hodgkins lymphomas and lymphomas in immunosuppressed individuals. It is believed that vaccination to prevent EBV infection, or post-infection vaccination in some form, could ultimately lead to the eradication or reduction in the incidence of these cancers. Our research activities are concerned with all aspects of the development of EBV vaccines and with trying to understand how EBV is regulated by the immune system. An EBV gp350 envelope glycoprotein vaccine originally developed here in Bristol has recently been shown to prevent infectious mononucleosis (glandular fever). We are also currently involved in a trial where a similar gp350 vaccine is being evaluated in EBV-seronegative paediatric organ transplant candidates. The aim is to prevent the B-cell lymphomas that frequently arise in these patients following primary EBV infection while immunosuppressed.
A second area of research has been concerned with the development of therapeutic vaccines to treat EBV-associated cancers and possibly other tumours. We have discovered that the EBV latent membrane protein LMP2 that is expressed on most EBV tumours is not efficiently processed and presented through the MHC class I pathway. LMP2-specific cytotoxic T-cells cannot normally kill B-cell and epithelial cell targets expressing this tumour antigen. However, they can be made "visible" to LMP2-specific cytotoxic T-cells by altering LMP2 processing and presentation using a non-toxic bacterial toxin derivative (see Ong et al., 2003 below) known as EtxB. Work is underway to develop recombinant EtxB as an immunotherapeutic for EBV-associated tumours.
A third area of activity has been to investigate the role of CD4+ T-cells in the control of EBV infection. We were one of the first laboratories to identify CD4+ T-cell activities that are important in EBV control (see Wilson and Morgan, 2002) and this field has now rapidly expanded. One important conclusion of this work is that CD4+ T-cells, paradoxically, can either kill EBV-infected B-cells or cause them to proliferate, depending on the initial CD4+ T-cell differentiation conditions. We are currently trying to determine exactly what these initial conditions are.
A fourth area of study has been the possible relationship between EBV infection and multiple sclerosis. To this end the levels of EBV neutralising antibodies in the serum of multiple sclerosis patients are being compared to matched controls.
Selected publications
- Morgan, A.J. and Poland, G (2011) The Jenner Society and the Edward Jenner Museum: Tributes to a physician-scientist. Vaccine. In press.
- Rodgers, V., Finn, A. and Morgan, A.J. (2010) Epstein Barr Virus (infectious mononucleosis) in 'Manual of childhood infections'. Oxford University Press.
- Poland, G.A. and Morgan, A.J. (2010) The Jenner Society: A new academic society for vaccinologists. Vaccine 28(28), 4439.
- Rees, L.E. Tizard, J., Morgan, A.J., Cubitt, D., Finerty, S., Oyewole-Eletu, T.A., Owen, K., Royed, C., Stevens, S.J., Shroff, R.C., Tanday, M.K., Wilson, A.D., Middeldorp, J.M., Amlot, P., Steven, N.M. (2009) A phase I trial of an Epstein-Barr virus gp350 vaccine for children with chronic kidney disease awaiting transplantation. Transplantation 88, 1025-1029.
- MacArthur, G.J., Wilson, A.D., Birchall, M.A. and Morgan, A.J. (2007) Primary CD4+ T-cell responses provide both helper and cytotoxic functions during EBV infection and transformation of fetal cord blood B-cells. J. Virol. 81(9), 4766-4775.
- Morgan, A.J. and Parker, S. (2007) Translational mini-review series on vaccines: The Edward Jenner Museum and the history of vaccination. Clinical and Experimental Immunology, 147 (3), 389-394.
- Borza, C.M., Morgan, A.J., Turk, S.M. and Hutt-Fletcher, L.M. (2004) Use of gHgL for attachment of Epstein-Barr virus to epithelial cells compromises infection. J. Virol. 78, 5007-5014.
- Guerreiro-Cacais, A.O., Li, L., Donati, D., Bejarano, M.T., Morgan, A.J., Masucci, M.G., Hutt-Fletcher, L. and Levitsky, V. (2004) The capacity of Epstein-Barr virus to infect monocytes and inhibit their development into dendritic cells is affected by the cell type supporting virus replication. J. Gen. Virol. 85, 2767-2778.
- Ong, K.W., Wilson, A.D., Hirst, T.R. and Morgan, A.J. (2003) The B subunit of Escherichia coli Heat-Labile Enterotoxin enhances CD8+ cytotoxic-T-lymphocyte killing of Epstein-Barr Virus-infected cell lines. J. Virol. 77(7), 4298-4305.