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Porcine Reproductive and Respiratory Syndrome (PRRS) Immunology

Our group

We 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. Our current research is 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.

Our aims

We are 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
  2. Induction of effector T cell-based immunity by viral vectored delivery of conserved vaccine candidate antigens
  3. Rational design of safer and more efficacious live attenuated vaccines

Our research

  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 a novel vaccine vector platform based on attenuated porcine cytomegalovirus.
  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
  4. Development of a Nipah virus vaccine to eliminate porcine reservoirs and safeguard human health. We are working with scientists within Pirbright and partners in the UK, Australia, Malaysia and India to develop a prototype vaccine that will protect pigs against Nipah virus that will aid the prevention and control of Nipah outbreaks.

Our impact

PRRSV is responsible for the most economically important infectious disease affecting the global pig industry. PRRS control is hampered by the rapid evolution of the virus and shortcomings with existing vaccines. By dissecting the pathological and protective immune responses evoked by PRRSV, we will be able to design safer and more effective vaccines. We will work with global animal health businesses to develop improved vaccines that will contribute towards improving animal welfare and enhancing the performance and sustainability of the pig industry both in the UK and overseas.

Group members

Franzoni G, Razzuoli E, Dei Giudici S, Carta T, Galleri G, Zinellu S, Ledda M, Angioi P, Modesto P, Graham S P, Oggiano A (2020)

Pathogens 9 (3) , 209
Graham S P, McLean R K, Spencer A J, Belij-Rammerstorfer S, Wright D, Ulaszewska M, Edwards J C, Hayes J W P, Martini V, Thakur N, Conceicao C, Dietrich I, Shelton H, Waters R, Ludi A, Wilsden G, Browning C, Bialy D, Bhat S, Stevenson-Leggett P, Hollinghurst P, Gilbride C, Pulido D, Moffat K, Sharpe H, Allen E, Mioulet V, Chiu C, Newman J, Asfor A S, Burman A, Crossley S, Huo J, Owens R J, Carroll M, Hammond J A, Tchilian E, Bailey D, Charleston B, Gilbert S C, Tuthill T J, Lambe T (2020)

npj Vaccines 5 (1) , 69
Holzer B, Rijal P, McNee A, Paudyal B, Clark B, Manjegowda T, Salguero F J, Bessell E, Schwartz J C, Moffat K, Pedrera M, Graham S P, Placido M B-D, La Ragione R M, Mwangi W, Beverley P, McCauley J W, Daniels R S, Hammond J, Townsend A R, Tchilian E (2020)

bioRxiv preprint , 2020.07.21.213470
McNee A, Smith T R F, Holzer B, Clark B, Bessell E, Guibinga G, Brown H, Schultheis K, Fisher P, Ramos S, Nunez A, Bernard M, Graham S, Martini V, Chrun T, Xiao Y, Kash J C, Taubenberger J K, Elliott S, Patel A, Beverley P, Rijal P, Weiner D, Townsend A, Broderick K, Tchilian E (2020)

Journal of Immunology 205 , 648-660
Pedrera M, Macchi F, McLean R K, Franceschi V, Thakur N, Russo L, Medfai L, Todd S, Tchilian E Z, Audonnet J-C, Chappell K, Isaacs A, Watterson D, Young P R, Marsh G A, Bailey D, Graham S P, Donofrio G (2020)

Vaccines 8 (1) , 115


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