Cytokines and synthetic double-stranded RNA augment the T helper 1 immune response of swine to porcine reproductive and respiratory syndrome virus

Abstract

Immunization of pigs with a modified live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine initially elicits a weak interferon (IFN)-gamma response. To improve the immune response, an adjuvant consisting of plasmid encoding either porcine interleukin (IL)-12 or IFN-alpha was co-administered during vaccination. In the presence of either adjuvant, at least a three-fold increase in the primary virus-specific IFN-gamma response was observed. While this enhancement was only transient (1 week) when the IL-12 expressing plasmid was used, the effect was not only still apparent at 6 weeks after vaccination in the presence of the IFN-alpha expressing plasmid but even after challenge with a virulent genetically divergent PRRSV. In contrast, no effect of either adjuvant on the production of anti-virus antibodies was noticed throughout the study. Despite the apparent augmentation of a T helper (Th) 1 type response by the inclusion of IFN-alpha or IL-12 during vaccination, this modulation did not necessarily correlate with a reduction in viremia. Since a similar increase in the degree of the IFN-gamma response to the PRRSV vaccine could be achieved by substituting polyinosinic-polycytidylic acid in lieu of either cytokine, exposure to PRRSV in the presence of a variety of Th 1 polarizing molecules can positively influence the development of the cell-mediated immune response of swine to this pathogen. Conceivably, such intervention could be applied to improve the formulation of anti-PRRSV vaccines.

Alternative codon usage of PRRS virus ORF5 gene increases eucaryotic expression of GP5 glycoprotein and improves immune response in challenged pigs

“…Further improvement might also be achieved with cytokine or cytokine-plasmid adjuvants [32][33][34]. Alternatively, it might be useful to increase the number of potential epitopes by coinjection of DNA plasmids carrying other PRRSV genes, since it has been previously described that epitopes of the GP4 of European strains are also involved in virus neutralisation [35], and that the M protein is the one mainly involved in the cellular immune response or cellular hypersensibility [36].…”

Effects of Porcine Reproductive and Respiratory Syndrome Virus-Infected Antigen-Presenting Cells on T Cell Activation and Antiviral Cytokine Production

“…Humoral and cell-mediated immune (CMI) responses to PRRSV are poor, compared with those to other swine viral pathogens, for example, pseudorabies virus and swine influenza virus (62). Specific antibodies to PRRSV detected by IDEXX Laboratories (Westbrook, ME) enzyme-linked immunosorbent assay (ELISA) appeared about 2 wk after infection (17,35,71). Neutralizing antibodies to PRRSV appeared about 4 wk after infection (71).…”

Construction and in vitro evaluation of a recombinant live attenuated PRRSV expressing GM-CSF

“…PRRSV infection could impair the ability of APCs to stimulate antigen-specific immune responses, dysregulate expression of various inflammatory cytokines, which could disrupt the establishment of an anti-virus microenvironment in vivo. Vaccines are widely used to control PRRSV; however, these vaccines can result in immunosuppression and confer limited heterologous protection [11][12][13]. As one of the most efficient adjuvants, GM-CSF has been widely studied to enhance the immunogenicity of tumor and pathogen antigens [14,16,[20][21][22][23][24][25].…”

“…Some examples are the partial protection against heterologous viruses [10], delayed and suboptimal cell-mediated immunity (CMI) and neutralizing antibody levels after vaccination [11][12][13].…”