Professor
Simon
Graham
I graduated with a first class BSc in Biological Sciences with Immunology Honours from the University of Edinburgh and went on to obtain a PhD from the Liverpool School of Tropical Medicine, where I developed a cattle model for testing experimental vaccines against onchocerciasis (river blindness). After post-doctoral positions working on Theilerioses vaccine development at the Centre for Tropical Veterinary Medicine, Edinburgh, and the International Livestock Research Institute, Kenya, I joined the Virology Department of the Animal and Plant Health Agency, Weybridge, leading immunological and vaccine-related research on a number of viral diseases of livestock. In September 2014, I took up the joint position of Group Leader PRRS Immunology at The Pirbright Institute and Senior Lecturer/Reader in Veterinary Immunology, within the School of Veterinary Medicine at the University of Surrey. In September 2019, I joined Pirbright on a full time basis and was appointed as a Visiting Professor at Surrey.
Porcine and bovine immunology; T cells, B cells and dendritic cells; monoclonal antibody discovery; identification and characterization of B and T cell antigens; vaccine development and evaluation of immune responses; novel vaccine delivery systems including viral vectors; porcine reproductive and respiratory syndrome viruses, pestiviruses and Henipaviruses.
I have a longstanding interest in understanding immunological mechanisms underlying protective immunity and the application of this knowledge to the development of new or improved vaccines. My current research is largely focused on the development of improved vaccines for the porcine reproductive and respiratory syndrome (PRRS). PRRS is arguably the most important infectious disease of pigs with a huge global economic impact. The PRRS virus (PRRSV) exists as two distinct species: 1 and 2. Both PRRSV species are rapidly diversifying and this is dramatically illustrated by the emergence of highly pathogenic PRRSV-2 variants that spread across Southeast Asia with devastating effects. However, emerging PRRSV-1 strains are also highly virulent, highlighting the risks posed to the UK pig industry. Vaccination is a key element to PRRS control and while both inactivated and live attenuated PRRS vaccines are widely used neither provides sufficiently effective protection against the diversity of circulating PRRSV strains. There is therefore an urgent need to develop more efficacious vaccines to aid PRRSV control.
I am working with colleagues and collaborators on three ambitious complimentary approaches aimed at the development of improved PRRS vaccines:
1. Develop broadly cross-protective vaccines based on highly conserved neutralising antibody targets: We are deploying cutting edge technologies to identify and characterise naturally occurring porcine monoclonal antibodies capable of broadly neutralising PRRSV strains. These antibodies will then be used to identify highly conserved vaccine targets that may be engineered to induce cross-protection.
2. Induction of effector T cell-based immunity by viral vectored delivery of conserved vaccine candidate antigens: Viral vector-based vaccines offer the potential to provide protection against virulent pathogens entering via the mucosal route. There is growing evidence that cell-mediated immune responses are critical for protection against PRRSV in the absence of neutralising antibodies. We have therefore identified and characterised conserved T cell antigens from PRRSV and are preparing to evaluate their vaccine potential using novel vaccine vector platforms.
3. Rational design of safer and more efficacious live attenuated vaccines: We are identifying the key determinants of PRRSV proteins that mediate immune evasion or contribute to disease. This will provide rational targets for the production of attenuated vaccine strains. We are also seeking to define virulence factors and are studying whether increased PRRSV virulence is associated with an enhanced capacity to infect and dysregulate dendritic cell function.
I am also leading a project to develop a vaccine that will protect pigs against Nipah virus that will aid the prevention and control of Nipah virus outbreaks.