Ceftiofur hydrochloride affects the humoral and cellular immune response in pigs after vaccination against swine influenza and pseudorabies

Abstract

Background: Cephalosporins are a class of antibiotics that are active against many Gram-positive and some Gram-negative bacteria. Beyond their antibacterial activity, they are reported to have various immunomodulatory properties. It has been shown that they reduce the secretion of cytokines as well as influence the humoral and cellular immune response. In the field conditions antibiotics are frequently administered at the same time as vaccines in pigs and, in the view of their potential immunomodulatory properties, it is important to examine their effect on the development and persistence of the post-vaccinal immune response. Ceftiofur is a very popular veterinary medicine third-generation cephalosporin with a broad spectrum of activity. It has been shown that it can inhibit cytokines secretion and in this way can potentially affect host immune response. The influence of ceftiofur on the immune response has not yet been investigated in pigs. In the present study we evaluated the influence of therapeutic doses of ceftiofur hydrochloride on the post-vaccinal immune response after vaccination with two model vaccines (live and inactivated).

Methods: Seventy pigs were divided into five groups: control, unvaccinated (C), control vaccinated against swine influenza (SI-V), control vaccinated against pseudorabies (PR-V), vaccinated against SI during ceftiofur administration (SI-CEF) and vaccinated against PR during ceftiofur administration (PR-CEF). Pigs from SICEF and PR-CEF groups received therapeutic dose of ceftiofur for five days. Pigs from SI-CEF, PR-CEF, SIV and PR-V groups were vaccinated against SI and PR. Antibodies to PRV were determined with the use of blocking ELISA tests (IDEXX Laboratories, USA). Humoral responses to SIV were assessed based on haemagglutination inhibition assay. T-cell response was analyzed with the use of proliferation test. The concentrations of IFN- γ and IL-4 in culture supernatant were determined with the use of ELISA kits Invitrogen Corporation, USA).

Results: The significant delay in the development of humoral response against pseudorabies virus (PRV) as well as a significant suppression of production of antibodies against swine influenza virus (SIV) was found in pigs receiving ceftiofur hydrochloride at the time of vaccination. The cellular immune response against PRV was also significantly affected by ceftiofur. In contrast, there were no significant differences between vaccinated groups with regard to the T-cell response against SIV. From day 28 of study to day 70, the concentration of INF-γ in culture supernatants were significantly lower in group treated with ceftiofur after restimulation with PRV. While, no significant differences were observed after restimulation of PBMC with H3N2 SIV.

Conclusions: The effect of an antibiotic therapy with ceftiofur hydrochloride on the humoral and cellular post-vaccinal immune responses in pigs was investigated. Ceftiofur hydrochloride was given in therapeutic doses. The results of the present study indicate that both, humoral and cell-mediated post-vaccinal immune responses can be modulated by treatment with ceftiofur hydrochloride. The results of our study point out that caution should be taken when administered this antibiotic during vaccination of pigs.

Fig. 1

The development and persistence of antibodies specific to gB of pseudorabies virus (PRV) and H3N2 swine influenza virus (SIV). PR-V- pigs vaccinated against pseudorabies, no treatment with antibiotic. PR-CEF - pigs received ceftiofur hydrochloride during vaccination against pseudorabies. SI-V- pigs vaccinated against swine influenza, no treatment with antibiotic. SI-CEF - pigs received ceftiofur hydrochloride during vaccination against swine influenza. C - control pigs (unvaccinated, no antibiotic treatment) . * - statistically significant differences between vaccinated groups

Fig. 2

The mean stimulation index values observed in pigs after vaccination against pseudorabies and swine influenza and in control, not vaccinated animals. The bold lines indicate border-line between nonspecific and antigen-specific proliferation. PR-V- pigs vaccinated against pseudorabies, no treatment with antibiotic. PR-CEF - pigs received ceftiofur hydrochloride during vaccination against pseudorabies. SI-V- pigs vaccinated against swine influenza, no treatment with antibiotic. SI-CEF - pigs received ceftiofur hydrochloride during vaccination against swine influenza. C - control pigs (unvaccinated, no antibiotic treatment). * - statistically significant differences between vaccinated groups

Fig. 3

Interferon-gamma (IFN-γ) secretion by peripheral blood mononuclear cells. The points represent the mean concentration of IFN-γ in culture supernatant after stimulation with pseudorabies virus (PRV) or swine influenza virus (SIV). PR-V- pigs vaccinated against pseudorabies, no treatment with antibiotic. PR-CEF - pigs received ceftiofur hydrochloride during vaccination against pseudorabies. SI-V- pigs vaccinated against swine influenza, no treatment with antibiotic. SI-CEF - pigs received ceftiofur hydrochloride during vaccination against swine influenza. C - control pigs (unvaccinated, no antibiotic treatment). * - statistically significant differences between vaccinated groups