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Title:   Author  item
                                            Brockmeier, Susanitem
                                            Loving, Crystalitem
                                            NELSON, ERIC - South Dakota State Universityitem
                                            Miller, Lauraitem
                                            Nicholson, Tracyitem
                                            Register, Karenitem
                                            Grubman, Marvinitem
                                            BROUGH, DOUGLAS - Genvec, Incitem
                                            Kehrli Jr, Marcus
  Submitted to: Clinical and Vaccine Immunology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 1/23/2012
                                    Publication  Date: 4/1/2012
                                    Citation: Brockmeier, S.L., Loving, C.L., Nelson, E.A., Miller, L.C., Nicholson, T.L., Register, K.B., Grubman, M.J., Brough, D.E., Kehrli, Jr., M.E. 2012. The presence of alpha interferon at the time of infection alters the innate and adaptive immune responses to porcine reproductive and respiratory syndrome virus. Clinical and Vaccine Immunology. 19(4):508-514.Interpretive Summary: Porcine reproductive and respiratory syndrome is one of the most devastating and costly diseases to the swine industry world-wide. Overall, the immune response to porcine reproductive and respiratory syndrome virus (PRRSV) is weak and results in delayed elimination of virus from the pig and inferior vaccine protection. Part of the reason for this inadequate immune response to PRRSV may be that it induces insufficient interferon alpha, which is an antiviral substance that the body naturally produces. In this study, pigs were given a harmless adenovirus that was engineered to deliver interferon at the same time that they were infected with PRRSV to determine the effects of interferon on viral infection and the immune response to PRRSV. The adenovirus was successful in increasing the level of interferon in the pigs for several days and the presence of the interferon at the time of infection had a positive effect by both reducing viral replication and enhancing the immune response to PRRSV, decreasing the severity of disease.
                                Technical Abstract: Porcine reproductive and respiratory syndrome (PRRS) is one of the most devastating and costly diseases to the swine industry world-wide. Overall, the adaptive immune response to PRRS virus (PRRSV) is weak and results in delayed elimination of virus from the host and inferior vaccine protection. PRRSV has been shown to induce a meager interferon (IFN)-alpha response, and in a previous study by our group, pigs that were injected with a nonreplicating human adenovirus type 5 vector expressing porcine IFN-alpha (Ad5-pIFN-alpha) and then challenged one day later with PRRSV had delayed viral replication and diminished disease severity. In this study, we followed the immune response in swine given Ad5-pIFN-alpha and challenged with PRRSV simultaneously. Not only was viremia delayed, but there was a decrease in viral load in the sera of pigs as well. Although seroconversion was slightly delayed in pigs receiving Ad5-pIFN-alpha, probably due to the delay in viremia, little difference was seen in the overall or neutralizing antibody response. However, there was an increase in virus-specific IFN-gamma secreting cells detected in the pigs receiving Ad5-pIFN-alpha, as well as an altered cytokine profile in the lung 14 days post-infection, indicating that the presence of IFN-alpha at the time of infection can alter the innate and adaptive immune response to PRRSV.


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