Cattle remain immunocompetent during the acute phase of foot-and-mouth disease virus infection

Abstract

Infection of cattle with foot-and-mouth disease virus (FMDV) results in the development of long-term protective antibody responses. In contrast, inactivated antigen vaccines fail to induce long-term protective immunity. Differences between susceptible species have also been observed during infection with FMDV, with cattle often developing persistent infections whilst pigs develop more severe symptoms and excrete higher levels of virus. This study examined the early immune response to FMDV in naïve cattle after in-contact challenge. Cattle exposed to FMDV were found to be viraemic and produced neutralising antibody, consistent with previous reports. In contrast to previous studies in pigs these cattle did not develop leucopenia, and the proliferative responses of peripheral blood mononuclear cells to either mitogen or third party antigen were not suppressed. Low levels of type 1 interferon and IL-10 were detected in the circulation. Taken together, these results suggest that there was no generalised immunosuppression during the acute phase of FMDV infection in cattle.

Figure 1

Cattle infected with FMDV were viraemic during acute infection and developed neutralising antibodies. A. Onset and duration of viraemia of all six FMDV challenged cattle used in this study as obtained by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). B. Neutralising antibody titre in serum of infected cattle. Sera with titres greater than or equal to 45 were considered to be positive (dotted line).

Figure 2

Total circulating leucocyte counts from all six FMDV challenged cattle (C1 to C6) during the acute phase of FMDV infection. Blood samples were collected into EDTA, and total leucocyte counts performed on the same day as collection. Counts were performed in triplicate on each sample. (N = 6) Lines show 2X STDEV of day 0.

Figure 3

Proliferative response of PBMC to mitogen during the acute phase of FMDV infection. PBMC from infected cattle were assayed for proliferation following in vitro incubation with Pokeweed mitogen and FMDV antigen in triplicate. Data shown is the mean of animals in each replicate (C1, C2 and C3 and C4 to C6) for each time point. Error bars show STDEV of all animals in each group for each time point.

Figure 4

Proliferative response to third party antigen during the acute phase of FMDV infection. PBMC from infected cattle (previously vaccinated with BHV) were assayed for proliferation following in vitro incubation with BHV antigen, in triplicate. Due to the variation in magnitude of response to BHV, the data are displayed separately for each of the cattle C1, C4, C5 and C6. Error bars show STDEV of the mean of three wells for each time point.

Figure 5

Proliferative response to FMDV antigen in vaccinated cattle. PBMC from five cattle vaccinated with FMDV O1 Manisa commercial vaccine were assayed for proliferative response to FMDV antigen. The kinetics of the proliferative response for each animal for the first 21 days post vaccination are shown. Error bars show STDEV for each of the five animals at each time point.

Figure 6

Type 1 IFN in sera of cattle during the acute phase of FMDV infection. Six cattle were assayed for circulating biologically active type 1 IFN by Mx CAT reporter assay.

Figure 7

IL-10 in sera of cattle during the acute phase of FMDV infection. Six cattle were assayed for circulating IL-10 by ELISA from day -2 to day 8 post infection. Data shown is the mean of all six animals (C1 to C6). Error bars show STDEV of the mean.