Construction of foot-and-mouth disease (FMD) virus-specific phage-display libraries and epitope identification for improved FMD vaccines generation

Foot-and-mouth disease (FMD) ranks as one of the most economically important infectious diseases of cloven-hoofed animals and is endemic in large regions of Africa, Asia and the Northern part of South America. The majority of FMD virus (FMDV)-neutralizing antibodies are directed against epitopes located on the surface-exposed capsid proteins. However, the location of these antigenic sites and their antigenic features may vary between the different strains. Antigenic variation results from changes to the viral capsid because of the high mutation rate of the virus such that each FMDV isolate is antigenically unique in its fine epitopic composition. This process leads to the generation of new variants circulating in the field, which may be different from those included in the vaccines. Therefore, vaccine efficacy and effectiveness of vaccination programs may be dramatically affected. Knowledge of the amino acid residues that comprise the antigenic determinants of FMD viruses is essential for the rational design of vaccine virus seeds that antigenically match circulating emerging or re-emerging strains, as well as induce a broad immunological response. Monoclonal antibodies, traditionally used for mapping of viral epitopes, have several limitations such as low throughput and high cost, which renders this technology unappealing. This project aims to identify critical antigenic determinants within the FMDV capsid from strains that circulate in different parts of the world, using newly developed assays. It will join the complementary expertise of four FMDV research institutes: ARC-OVR (South Africa), the Pirbright Institute (UK), INTA (Argentina) and the University of Glasgow (UK). We aim to use a library of recombinant “mini”-antibodies generated from FMDV-immune buffalos and cattle by making use of a phage-display library technology, which has been extensively and successfully used by ARC-OVR. This joint-project will provide important information by identifying critical FMDV epitopes, unique or shared among different strains, which can be implemented to produce improved vaccines.