The severity of the acute form of CSF is responsible for the high mortality rate and has been the subject of many studies. Nevertheless, some animals are likely to develop a mild, chronic, or unapparent form of the disease. Paradoxically, this clinical form of the disease has not been well studied, especially regarding its pathogenesis. In this study, we investigated the infection in domestic pigs that is caused by the CSFV Cat01 strain, which is responsible for the 2001-2002 CSFV outbreak in Catalonia, Spain, and which caused mild and nonspecific clinical signs compared to the infection that is caused by another CSFV strain that is responsible for inducing severe clinical symptoms of disease. We assessed the impact of the CSFV infection in the immune system of domestic pigs, mainly on the kinetics of different cytokines, such as IFN-α (innate immunity) and IFN-γ (adaptive immune response), during the first weeks after infection. In addition, we evaluated the impact on the induction of the humoral response and its relation to the course of infection and the RNA CSFV viral load. The IFN-α levels in the serum samples from the pigs that developed a milder form of the CSF disease (infected with Cat01 strain) were lower than those that were detected in the pig with severe clinical CSF signs (Margarita strain). After infection with Cat01 strain, the IFN-γ levels in response to CSFV were detected in addition to the humoral response. Interestingly, in the serum samples of these animals, we detected the lowest load of CSFV RNA. Similarly, the lowest viral load levels were detected in the tonsils of these pigs. Both the T cells and the humoral response that were generated in most of the pigs that were infected with strain Cat01 may be related to the protection in the symptom progression of CSF against this viral strain. These results explain the antiviral role of IFN-γ in the absence of an antibody response. Likewise, these results corroborate the relevance and relationship that exists between the intensity of the T cell response and the protection against CSFV replication. Additionally, these results also explain how the failure to induce optimal levels of humoral and cellular responses after CSFV infection promotes the spread and persistence of the virus.
To cite this version:J. Tarradas, J.M. Argilaguet, R. Rosell, M. Nofrarías, E. Crisci, et al.. Interferon gamma induction correlates with protection by DNA vaccine expressing E2 glycoprotein against classical swine fever virus infection in domestic pigs. Veterinary Microbiology, Elsevier, 2010, 142 (1-2) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. an inverse correlation seemed to exist between early induction of IFN-alpha and the protection observed, 44 while IL-10 seemed to be differentially regulated in vaccinated and non-vaccinated animals. 45Our results support the relevance of the induction of a strong T cellular response to confer a 46 solid protection upon DNA vaccination against CSFV. Further experiments are needed to be done in 47 order to clarify the key cytokines playing a role in CSFV-protection and to obtain emergency vaccines 48 capable to confer robust and fast protection.
Three peptide-based systems integrating B and T antigenic sites of CSFV and displaying the B epitopes in fourfold presentation have been designed and produced, and shown to bring about significant enhancements in immunogenicity over the peptides in monomeric form. Of the different strategies tested for producing the dendrimeric constructs, stepwise SPPS using 3,6-dioxaoctanoic acid as flexible, PEG-like spacer units at the branching points is clearly advantageous, in particular over ligation in solution. The constructs have been used for immunization of domestic pigs, in order to evaluate the protective response induced by each peptide constructs, and to characterize the B- and T-cell response against CSFV in the natural host.
The reduction of antimicrobial resistance is a major challenge for the scientific community. In a few decades, infections by resistant bacteria are forecasted to be the main cause of death in the world. The withdrawal of antibiotics as growth promoters and their preventive use in animal production is essential to avoid these resistances, but this may impair productivity and health due to the increase in gut inflammation. This reduction in productivity aggravates the problem of increasing meat demand in developing countries and limits the availability of raw materials. Probiotics are promising products to address this challenge due to their beneficial effects on microbiota composition, mucosal barrier integrity, and immune system to control inflammation. Although many modes of action have been demonstrated, the scientific community is not able to describe the specific effects that a probiotic should induce on the host to maximize both productivity and animal health. First, it may be necessary to define what are the innate immune pathways acting in the gut that optimize productivity and health and to then investigate which probiotic strain is able to induce the specific effect needed. This review describes several gaps in the knowledge of host-microbiota-pathogen interaction and the related mechanisms involved in the inflammatory response not demonstrated yet in poultry.
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