Molecular, antigenic and vaccine matching studies, including protective response in vivo, were conducted with a foot-and-mouth disease type O virus isolated during the outbreak in September 2011 in San Pedro, Paraguay, country internationally recognized as free with vaccination in 1997. The phylogenetic tree derived from complete VP(1) sequences as well as monoclonal antibody profiling indicated that this isolate was related to viruses responsible for previous emergencies in free areas of the Southern Cone of South America occurring sporadically between the years 2000 and 2006. Marked differences with the vaccine strain O(1)/Campos, including the loss of reactivity with neutralizing MAbs, were recognized. Levels of protective antibodies induced by the vaccine containing the O(1)/Campos strain against the San Pedro virus and the virus responsible for the previous emergency in 2006 in the Southern Cone assessed by in vitro vaccine matching studies pointed to an insufficient protective response 30 days after vaccination (DPV), which was properly attained at 79 DPV or after revaccination. In agreement with the in vitro assessment, the in vivo challenge in the Protection against Podal Generalization test in cattle indicated appropriate protection for the San Pedro strain at 79 DPV or after revaccination. The complementary conclusions that can be derived from vaccine matching tests designed differently to fit the various objectives intended: prophylaxis, emergency vaccination or incorporation of new field strains into antigen banks, is evaluated. This is the first report of the antigenic and immunogenic characterization of the variants responsible for emergencies in the Southern Cone of South America and the putative impact of the changes on the cross protection conferred by the vaccine strain.

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