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Abstract: Deoxynivalenol (DON), a mycotoxin produced by some Fusarium species, is a frequent contaminant of cereals. This toxin is known to modulate the immune function but only few studies have investigated the effect of DON on the vaccinal immune response. In the present experiment, 24 pigs received for 9 weeks either control feed or feed naturally contaminated with 2.2–2.5mgDON/kg feed. At days 4 and 15 of the experiment, the animals were subcutaneously immunized with ovalbumin. Consumption of DON-contaminated diet does not have a major effect on the hematological and biochemical blood parameters. By contrast, ingestion of DON significantly affects the global and the specific immune response of the pigs. In the serum, DON increases the concentration of total IgA and, in vaccinated animals, DON also increases the concentration of ovalbumin-specific IgA and IgG. DON does not modulate lymphocytes proliferation after mitogenic stimulation but the toxin had a biphasic effect on lymphocyte proliferation after antigenic stimulation (up-regulation at day 21 and down-regulation at day 35–49). Because cytokines play a key role in immunity, the expression levels of TGF-β, IFN-γ, IL-4 and IL-6 were measured, by RT-PCR in the spleen, the ileum and the mesenteric lymph node of the animals at the end of the experiment. In the mesenteric lymph node, a significantly lower expression of both TGF-β and IFN-γ mRNA expression levels is observed in animals feed with DON when compared with control piglets. Taken together, our data indicate that DON alters the vaccinal immune response. These results may have implications for humans and animals consuming DON-contaminated food or feed as breakdown in vaccinal immunity may lead to the occurrence of disease even in properly vaccinated populations. [Copyright &y& Elsevier]