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Foot-and-mouth disease virus (FMDV) continues to be a significant economic problem worldwide. Control of the disease involves the use of killed-virus vaccines, a control measure developed decades ago. After natural infection, the primary site of replication of FMDV is the pharyngeal area, suggesting that a mucosal immune response is the most effective. Humoral immunity to killed-virus vaccination induces antibodies that can prevent the clinical disease but not local infection. Determining whether infection or vaccination stimulates IgA-mediated local immunity depends on the method of analysis. Different assays have been described to analyze the quality of antibody responses of cattle and swine to FMDV, including indirect double-antibody sandwich enzyme-linked immunosorbent assay (IDAS-ELISA) and antibody capture assay-ELISA (ACA-ELISA). We tested these assays on swine and show that vaccinated animals had FMDV-specific IgM and IgG but no IgA in either serum or saliva. After the infection, both assays detected FMDV-specific IgM, IgG, and IgA in serum. Notably, serum IgA was more readily detected using the ACA-ELISA, whereas IgA was not detected in saliva with this assay. FMDV-specific IgA antibodies were detected in saliva samples using the IDAS-ELISA. These data show that parenterally administered, killed-virus vaccine does not induce a mucosal antibody response to FMDV and illuminates limitations and appropriate applications of the two ELISAs used to measure FMDV-specific responses. Further, the presence of the IgA antivirus in serum correlates with the presence of such antibodies in saliva.

The role of dendritic cells (DC) in the initiation of immune responses against foot-and-mouth disease virus (FMDV) is poorly understood. We analyzed the innate response of freshly isolated swine skin DC to the virus and show a rapid induction of beta interferon (IFN-beta) mRNA but not IFN-alpha mRNA. However, these DC secreted both IFN-alpha and IFN-beta proteins in response to live virus but not killed virus. Furthermore, the surface expression of swine major histocompatibility complex class II (SLA II) or CD80/CD86 molecules and antigen processing functions were not affected by FMDV exposure. Given the demonstrated sensitivity of FMDV to IFN-alpha/beta, there was no productive or nonproductive infection of these cells. Finally, freshly isolated skin DC constitutively expressed intracellular IFN-alpha protein in the absence of stimulation, with no detectable secretion of the cytokine until virus exposure. In situ analysis of these DC showed that these cells express and store IFN-alpha in uninfected animals. This is the first demonstration of the constitutive expression of IFN-alpha in resident, tissue-derived DC and indicates that skin DC can play an important role in the innate immune response of swine to viral infections.