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Characterization of Cytotoxic T Lymphocyte Function After Foot-and-Mouth Disease Virus Infection and Vaccination

Patch, Jared R., Kenney, Mary, Pacheco, Juan M., Grubman, Marvin J., Golde, William T.
Viral Immunology 2013 v.26 no.4 pp. 239
Adenoviridae, Foot-and-mouth disease virus, antigens, cell-mediated immunity, cross reaction, cytotoxic T-lymphocytes, foot-and-mouth disease, genetic vectors, major histocompatibility complex, neutralizing antibodies, recombinant vaccines, swine, vaccination, viral shedding, viremia, viruses
Foot-and-mouth disease (FMD) is an economically important disease of cloven-hoofed animals that remains a global threat to livestock species. The induction of neutralizing antibodies against FMD virus (FMDV) has been the central goal of vaccination efforts against this disease. Although these efforts have yielded much success, challenges remain including lack of cross-neutralizing antibodies, poor induction of cellular immune responses, and inadequate duration of immunity. Despite their prominent role in anti-viral defense, the role of cytotoxic T lymphocytes (CTL) in FMDV immunity has not been defined. We previously developed an assay for detection of CTL cytolytic activity and demonstrated that a modified adenovirus-vectored FMDV vaccine could induce CTL activity. In this present study, we now report induction of FMDV specific CTL responses following infection of pigs with virulent FMDV strain A24. Further, we tested whether the induction of CTLs specific for FMDV following targeted vaccination could protect against challenge with FMDV. The CTL response against FMDV in the absence of significant neutralizing antibody failed to protect against clinical disease. However, clinical disease was delayed and viremia was suppressed compared to control animals, suggesting a role for CTLs in the control of virus shedding. This CTL induction was under the artificial condition of limiting T cell help for the CD8+ CTLs, as antigen was targeted to class I MHC by the vaccine strategy, in part to limit induction of an antibody response. These results provide new insights showing induction of CTL responses to FMDV can be achieved by vaccination, creating the potential for improving vaccine performance by targeting cellular immunity.