A DISSERTATION SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE IN ONE HEALTH MOLECULAR BIOLOGY OF SOKOINE UNIVESITY OF AGRICULTURE. MOROGORO, TANZANIAFoot-and-mouth disease (FMD) is a highly contagious disease of cloven hooved animals that continues to occur in Ngamiland District of Botswana although stringent disease control measures have been put in place. This may be due to irrelevance of currently used vaccine strains. In the present study, genetic and antigenic characteristics of SAT2 viruses isolated from outbreaks which occurred in 2011 and 2015 in Ngamiland districtwere examinedin order to determine any mutational changes of the FMD viruses circulating in that area. The antigenic relationships between the outbreak strains and SAT2 vaccine strains currently used were also determined. Tissue samples collected were subjected to sequencing of the VP1 gene, phylogenetic analysis and vaccine matching with the two SAT2 vaccines strains currently in use in the same region; SAT251 and SAT2035. There was almost 100% amino acid sequence similarity within both outbreaks while minimal mutations (90% sequence similarity) occurred between the outbreaks. Phylogenetic analysis revealed that both outbreaks were caused by genetically similar viruses that belong to SAT2 topotype III. The newer vaccine strain, SAT2035 clustered with the field virus isolates on the phylogenetic tree indicating that it also belongs to the same topotype. However, the older vaccine strain, SAT251, was shown to belong to topotype II. Amino acid variation analysis revealed that mutations occurred post the 2011 outbreak but did not impact on the antigenicity of the field isolates although majority of variability occurred at known FMDV antigenic sites. This is confirmed by r1values obtained against both vaccine strains. The findings are evidence that the vaccines provide satisfactory immunity and are still relevant to confer protection against circulating field strains in the area because minimal mutationsoccurred intra- and inter-outbreaks. Recurrence of the disease is probably due to low vaccination coverage and this should be improved.