Improved vaccines for foot-and-mouth disease control : evaluation of a chimera-derived FMD vaccine in relation to a current SAT type vaccine

Abstract

Foot-and-mouth disease virus (FMDV), a member of the Picornaviridae, causes a highly contagious disease that affects cloven-hoofed animals and leads to production losses, especially in intensive farming systems. In sub-Saharan Africa, control of the disease is complicated by the extensive variability of the South African Territories (SAT) type viruses, which exist as distinct genetic and antigenic variants in different geographical regions. Improved control of FMD, therefore, requires vaccines to be custom-made to specific geographical areas. In this regard, a potentially powerful approach involves the engineering of chimeric FMDV of which the antigenic properties can be readily manipulated. Consequently, the aim of this study was essentially to evaluate a custom-engineered chimeric FMD vaccine in relation to a current SAT type vaccine. To enable the selection of vaccine strains that would provide the best vaccine match against emerging viruses, phylogenetic, genetic and antigenic analyses of SAT serotypes prevalent in sub-Saharan Africa was performed. The results indicated that although SAT1 and SAT2 viruses displayed similar genetic variation within each serotype, antigenic disparity, as measured by r1-values, was less pronounced for SAT1 viruses compared with SAT2 viruses. Consequently, the SAT1 virus KNP/196/91 was selected and a cross-serotype chimeric virus, vKNP/SAT2, was engineered by replacing the external capsid-encoding region (1B-1D/2A) of an infectious cDNA clone of the SAT2 vaccine strain, ZIM/7/83, with that of KNP/196/91. The population diversity of the cell-adapted chimeric virus and pig-adapted KNP/196/91 virus was investigated by means of pyrosequencing; the results of which indicated that the population diversity of the respective viruses was indeed comparable to each other. Subsequently, chemically inactivated vaccines were produced from intact 146S virion particles of both the chimeric and parental viruses and evaluated in a full potency test. Pigs vaccinated with the chimeric vaccine produced neutralising antibodies and showed protection against homologous FMDV challenge. Cumulatively, the data provide support that chimeric vaccines containing the external capsid of field isolates can be successfully produced and that they induce protective immune responses in FMD host species. The potential therefore exists to generate more effective newgeneration chemically inactivated-FMD vaccines that are custom-engineered and specifically produced for geographical areas.