The main focus of our research is the development of efficacious, safe vaccination strategies against African horse sickness virus (AHSV) and bluetongue virus (BTV).
AHSV and BTV are members of the Genus Orbivirus, Family Reoviridae that infect equids and ruminants respectively, causing severe disease and huge economic loses to the equine and farming industries. For this reason, African horse sickness and bluetongue are listed diseases of the OIE (World Organisation for Animal Health) and are notifiable in most countries.
Vaccination is key for the control of AHSV and BTV, but its efficacy is hampered by the antigenic variability and structural complexity of the main viral protective antigens. In addition, widespread control campaigns with conventional vaccines interfere with serological surveillance and make it difficult to demonstrate the disease status in a particular country. This is particularly relevant for notifiable diseases that have high impact on international trade of livestock.
Our aim is to gain further understanding of the effector mechanisms of immunity of the mammalian host against AHS and BTV. Specifically, we focus on mechanisms of virus neutralisation by antibodies, the epitope structure of the protective antigens of AHSV and BTV and how to mimic these complex antigens in order to develop safe efficacious vaccines. AHSV and BTV are antigenically variable (AHSV has 9 serotypes; BTV has 26 serotypes) and protective immunity is serotype-specific. Improving our knowledge of the epitope structure of AHSV and BTV will enable the development of cross-reactive vaccines and passive immuno-therapeutics.
We are currently exploring different recombinant DNA technologies and antigen delivery mechanisms (i.e. baculovirus expression, DNA vaccination, viral vector vaccination, reverse genetics) to develop these type of vaccines. One objective of our research is to characterise the effector mechanisms of immunity induced by these different vaccination platforms. These technologies enable the development of a DIVA (Differentiation of Infected from Vaccinated Animals) strategy, which would facilitate disease surveillance, international trade and eradication.
We are currently working on the development of viral vector vaccines for AHS, using modified Vaccinia Ankara as a model. This work, funded by Defra and partially by the Genomia Foundation, showed that a vaccine expressing the VP2 protein of AHSV (MVA-VP2) can induce an antibody response that confers complete clinical protection in a mouse model and also in the target species. This MVA-VP2 vaccine strategy was also successful with BTV. In addition, we showed that single serotype-specific MVA-VP2 can be administered as a polyvalent vaccine inducing a cross-reactive antibody response. Furthermore, in collaboration with the Jenner Institute in Oxford, we are investigating the use of viral vector vaccines to express two, three or four AHSV proteins, to enhance cross-reactivity, duration and magnitude of the immune responses against AHSV.
Alternative vaccine delivery platform technologies are being investigated in collaboration with Oxford-Brookes University and the University of Queensland.
The AHS vaccine strategy we are working on has DIVA capacity when used in conjunction with existing serological and molecular diagnostic tests, based on antigens different to those included in the vaccine. These DIVA vaccines would protect equine populations against AHS without compromising diagnosis, surveillance and import-export testing and would facilitate the adoption of regionalisation and eradication policies.
The potential advantages of this type of DIVA AHSV vaccines have been acknowledged by the OIE, which recommended, in its Regional Meeting for North Africa and the Middle East celebrated in Dubai in 2014, their further development and eventual commercialisation.