African swine fever virus: Development of vaccines and epidemiological investigations. (360G-Wellcome-075813_C_04_Z)

The goal of this project is the control of African Swine Fever Virus (ASFV) through construction and testing of recombinant and attenuated virus vaccines. Many recent outbreaks of ASF have caused devastating losses to both rural poor and commercial farms. There is no vaccine and control relies on rapid diagnosis and implementation of sanitary measures and movement restrictions. In addition a number of problems, such as persistent infections in domestic pigs and wild life reservoirs and vectors, complicate the control of ASF. An effective vaccine would help to control a major pathogen of pigs in large endemic areas of Africa, provide an alternative to the mass slaughter of animals, and protect elsewhere from accidental entry of the virus. Two vaccine designs will be developed. Both are based on delivery to macrophages/antigen- presenting cells in order to stimulate all arms of the immune response. The first is based on three defined proteins (p30, p54 & p72) that stimulate immunity through the production of neutralising antibodies. Here, targeting of the vaccine is achieved by (a) insertion of the virus proteins into the approved Aujezsky's veterinary virus vaccine and (b) construction of a fusion protein comprising the virus protein and the Fv fragment of an anti-porcine MHC class II monoclonal antibody. The second vaccine approach takes into account the reported multiple mechanisms and determinants of immunity, and is based on the construction of nonpathogenic, attenuated ASFV mutants with host genes for virulence or modification of host immune responses deleted. As a parallel and complementary approach to this a replication deficient ASFV will be constructed. Initial testing of virus vaccines will be done in vitro to assess replication efficiency and impact on host cell transcription profiles. Pilot experiments on pigs will then establish which vaccines proceed to evaluation through full scale vaccination and challenge. An investigation of the anti-ASF immune responses in these experiments may provide indicators of protective immunity, which will be useful in the future. The project brings together the major European laboratories who have made significant contributions to the field, together with the main OIE reference lab. in South Africa where the disease is endemic and where there is sufficient infrastructure, not only to contribute to the project, but also to benefit from training opportunities. In particular, the general approaches to be followed are applicable to many other infectious diseases, both medical and veterinary.