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Research Project: Intervention Strategies to Support the Global Control and Eradication of Foot-and-Mouth Disease Virus(FMDV)

Location: Foreign Animal Disease Research

Title: Expanding specificity of class 1 restricted CD8+ T cells for viral epitopes following multiple inoculations of swine with a human adenivorus vectored foot-and-mouth disease virus (FMDV) vaccine

item Pedersen, Lasse - Technical University Of Denmark
item Patch, Jared - University Of Vermont
item Kenney, Mary
item Glabman, Raisa - University Of Vermont
item Nielsen, Morten - Technical University Of Denmark
item Jungersen, Gregers - Technical University Of Denmark
item Buus, Soren - University Of Copenhagen
item Golde, William

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/16/2016
Publication Date: 11/15/2016
Citation: Pedersen, L.E., Patch, J.R., Kenney, M.A., Glabman, R., Nielsen, M., Jungersen, G., Buus, S., Golde, W.T. 2016. Expanding specificity of class 1 restricted CD8+ T cells for viral epitopes following multiple inoculations of swine with a human adenivorus vectored foot-and-mouth disease virus (FMDV) vaccine. Veterinary Immunology and Immunopathology. 181:59-67. doi: 10.1016/j.vetimm.2016.07.012.

Interpretive Summary: The best response to vaccination against viral infections includes both a humoral, immune response, characterized by production of anti-virus specific antibody and a cellular immune response. Cellular responses are the activation and expansion of T lymphocytes specifically reactive to viral derived proteins that can use that reactivity to identify and kill virus infected cells. Vaccines that protect against viral infections have different formulations or “vaccine platforms”. Some vaccines are subunit, recombinant or killed virus vaccines, where safety against transmission of the virus can be tested and documented. Specifically, there are no live virus components of the vaccine. These vaccines are excellent for inducing an antibody response, but such responses have limited cross-reactivity for diverse virus isolates and these vaccines do not induce a cellular immune response. Live attenuated vaccines are living viruses that lack the virulence that the virus needs to cause disease. These have very similar life cycles to the pathogenic virus, and as such can induce both humoral and cellular responses effectively. However, these live vaccines can “revert” to virulence and again cause disease, therefore they are not as safe as other vaccine platforms. We tested a strategy of combining a vaccine that stimulates an excellent humoral response, the recently licensed adenovirus vectored foot-and-mouth disease (FMD) vaccine (Ad-FMD) with a new vaccine that uses the same adenovirus to deliver T cell antigens, termed Ad-FMDV-T. We have previously published that Ad-FMDV-T can induce a cellular immune response. Now we report that multiple vaccinations of individual pigs results in the expansion of the antigen specificity of the response. This expanded specificity can be manipulated to create vaccines that have a broader cross reactivity resulting in better protection. This technology would be particularly valuable if it can be applied to other virus vaccines, including human virus vaccines such as influenza vaccines.

Technical Abstract: The immune response to the highly acute foot-and-mouth disease virus (FMDV) is routinely reported as a measure of serum antibody. However, a critical effector function of immune responses combating viral infection of mammals is the cytotoxic T lymphocyte (CTL) response, mediated by virus specific CD8 expressing T cells. This immune mechanism arrests viral spread by killing virus infected cells before new, mature virus can develop. We have previously shown that infection of swine by FMDV results in a measurable CTL response and have correlated CTL killing of virus-infected cells with specific class I MHC tetramer staining. In this report, we show that the specificity of the CD8 T cell response to a modified replication defective human adeno5 virus vector (Ad5) FMDV vaccine varies between cohorts of genetically identical animals. Further, we demonstrate epitope specificity of CD8 T cells expands following multiple immunizations with such adeno5 virus vector expressing the structural proteins of FMDV.