Submitted to: Clinical and Vaccine Immunology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 1/15/2010
Publication Date: 4/1/2010
Citation: Pacheco Tobin, J., Butler, J.E., Jew, J., Ferman, G.S., Zhu, J.J., Golde, W.T. 2010. IgA antibody response of swine to foot-and-mouth disease virus (FMDV) infection and vaccination. Clinical and Vaccine Immunology. 17(4):550-558. Interpretive Summary: Protection against foot-and-mouth disease virus (FMDV) infection is mediated, at least in part, by antibody. This virus spreads by aerosol and the primary site of infection is the upper respiratory tract. Vaccines are available that can protect against disease but not infection of animals exposed to virus. In these studies, we show the difficulty in analyzing the quality of the antibody response and how that quality is different between animals infected with FMDV verses animals vaccinated and then challenged. Specifically, antibody in nasal secretions and saliva (mucosal antibody) is lacking in vaccinated animals whereas animals infected with virus have a strong anti-FMDV mucosal antibody response. These results indicate a need to develop vaccines that induce mucosal antibody responses to FMDV.
Technical Abstract: 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. However, the primary site of replication of FMDV after natural infection is the pharyngeal area and it can be assumed that mucosal immunity would be important. The humoral immune response to vaccination with killed vaccine induces circulating antibodies that can prevent the clinical disease but do not prevent local primary infection. Determining whether infection or vaccination stimulates immunoglobulin-A-mediated (IgA-mediated) local immunity can depend on the assay used. Different assays have been described to analyze the quality of antibody responses of cattle and swine to FMDV. One Enzyme-linked immunosorbent assay (ELISA) format, termed indirect double antibody sandwich (IDAS-ELISA), theoretically allows for the detection of all antibodies according to isotype that are reactive with the immobilized virus. The alternative, antibody capture assay (ACA-ELISA) first captures all of a particular Ig isotype and then allows those that are virus-specific to capture virus and be subsequently detected. Here, we tested these assays and show that vaccinated animals had FMDV-specific IgM and IgG but no IgA in either serum or saliva samples. After infection, both assays detected FMDV-specific IgM, IgG, and IgA in serum. Notably, serum IgA was more readily detected using the ACA-ELISA, which avoids inter-isotype competition. IgA was not detected in saliva after vaccination by either assay but after challenge, saliva samples had readily detectable levels of FMDV-specific IgA antibodies when tested using IDAS-ELISA, but not the ACA-ELISA. Our 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.