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Title: Systemic immune response and virus persistence after foot-and-mouth disease virus infection of naïve cattle and cattle vaccinated with a homologous adenovirus-vectored vaccine

item ESCHBAUMER, MICHAEL - Oak Ridge Institute For Science And Education (ORISE)
item STENFELDT, CAROLINA - Oak Ridge Institute For Science And Education (ORISE)
item REKANT, STEVEN - Oak Ridge Institute For Science And Education (ORISE)
item Pacheco Tobin, Juan
item Hartwig, Ethan
item Smoliga, George
item Kenney, Mary
item Golde, William
item Rodriguez, Luis
item Arzt, Jonathan

Submitted to: BioMed Central (BMC) Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/10/2016
Publication Date: 9/15/2016
Citation: Eschbaumer, M., Stenfeldt, C., Rekant, S.I., Pacheco Tobin, J., Hartwig, E.J., Smoliga, G.R., Kenney, M.A., Golde, W.T., Rodriguez, L.L., Arzt, J. 2016. Systemic immune response and virus persistence after foot-and-mouth disease virus infection of naïve cattle and cattle vaccinated with a homologous adenovirus-vectored vaccine. BioMed Central (BMC) Veterinary Research. 12:205.

Interpretive Summary: Foot-and-mouth disease (FMD) is the most important transboundary disease limiting the international trade of livestock. It is well known that after an acute infection with FMD virus (FMDV), some cattle recover completely, whereas others go on to become silent carriers of the virus. However, it is not known how the fate of any individual cow is decided. In this study, we infected 47 Holstein steers with foot-and-mouth disease virus (18 with, and 29 without prior vaccination). Before and after the infection, we examined many facets of the steers’ immune systems (interferon activity, white blood cells, antibodies, etc.), to find differences between eventual carriers and non-carriers. Of the 18 non-vaccinated animals, 62 percent became persistently infected, compared to 55 percent of the 29 vaccinated animals. Additionally, there were distinct patterns in the immune response to infection between vaccinated and non-vaccinated animals. After infection with FMDV, vaccinated animals had increased levels of immune cells in their blood, while fewer of these cells were circulating in non-vaccinated animals. At the same time, we measured high levels of interferon in the animals that had not been vaccinated which was not detectable in vaccinated animals. These findings do not immediately explain the phenomenon of FMDV persistence, but does provide important information toward an improved understanding of how the bovine immune system responds to the infection.

Technical Abstract: In order to investigate host factors associated with the establishment of persistent foot-and-mouth disease virus (FMDV) infection, the systemic immune response to vaccination and challenge was studied in 47 Holstein steers. Eighteen steers which had received one dose of recombinant FMDV A vaccine two weeks earlier, and 29 non-vaccinated steers were challenged by intra-nasopharyngeal deposition of FMDV A24 Cruzeiro. For up to 35 days after challenge, host factors including type I/III interferon (IFN) activity, complete blood counts, T lymphocyte subsets, neutralization titers, FMDV-specific antibody, and antibody-secreting cells were characterized in the context of viral infection dynamics. Vaccination induced a strong antibody response. FMDV-specific IgM in vaccinated animals did not increase further after challenge, while there was a transient peak of FMDV-specific IgM in non-vaccinated animals. Both groups had a lasting increase of specific IgG and neutralizing antibody after challenge. Substantial IFN activity in non-vaccinated animals coincided with viremia and no systemic IFN or viremia was detected in vaccinated animals. Circulating lymphocyte and monocyte counts in vaccinated animals transiently increased after challenge, whereas lymphocytes decreased in non-vaccinated animals, coincident with viremia, increased IFN activity, and clinical disease. The CD4 positive/CD8 positive T cell ratio in blood of non-vaccinated animals was transiently increased during acute infection, driven by an absolute decrease of CD8 positive T cells. The incidence of persistent infection was 61.5 percent in non-vaccinated and 54.5 percent in vaccinated animals. Overall, the systemic factors examined were not significantly associated with the carrier/non-carrier divergence; however, significant differences were identified between responses of non-vaccinated and vaccinated cattle.