BackgroundDue to difficulties in eradicating porcine reproductive and respiratory syndrome (PRRS) linked to biosecurity challenges, transmission of the virus and the lack of efficient DIVA vaccines, successful control of PRRS requires a combination of strict management measures and vaccination of both sows and piglets. The present study aimed to assess the efficacy of a recently developed MLV vaccine (Ingelvac PRRSFLEX® EU) in piglets at 2 and 3-weeks of age in the presence of homologous maternally derived antibodies as the dams were vaccinated with the same vaccine strain (ReproCyc® PRRS EU).MethodsThe study was carried out on a Hungarian farrow to finish farm naturally infected with PRRSv. The study was designed as a blind, placebo controlled side by side trial. ORF5 sequence similarity of the vaccine strain and the resident field strain was 87.8 %. PRRS specific real-time quantitative PCR was performed from serum samples to measure both the viral load and the frequency of virus positive animals.ResultsAt the time of the natural infection observed in the control group at 10–12 weeks of age, the number of viraemic animals did not increase significantly in the vaccinated group. To understand the infection dynamics, positive PCR samples with low Ct values were sequenced (ORF5) and the data analysis indicated the circulation of wild type virus in both groups, however wild type virus was only found in non-vaccinated animals.ConclusionsOur data indicate that piglets vaccinated at as early as 2 weeks of age with Ingelvac PRRSFLEX® EU were protected both in terms of proportion of viraemic animals and viraemia levels. It has to be highlighted that these results were achieved in piglets with high levels of homologous maternally derived antibodies (MDA) at the time of vaccination.
Both authors contributed equally to this work. ‡ Both authors share last authorship.Donor alloantigen infusion induces T cell regulation and transplant tolerance in small animals. Here, we study donor splenocyte infusion in a large animal model of pulmonary transplantation. Major histocompatibility complex-mismatched single lung transplantation was performed in 28 minipigs followed by a 28-day course of methylprednisolone and tacrolimus. Some animals received a perioperative donor or third party splenocyte infusion, with or without low-dose irradiation (IRR) before surgery. Graft survival was significantly prolonged in animals receiving both donor splenocytes and IRR compared with controls with either donor splenocytes or IRR only. In animals with donor splenocytes and IRR, increased donor cell chimerism and CD4 + CD25 high+ T cell frequencies were detected in peripheral blood associated with decreased interferon-c production of leukocytes. Secondary third-party kidney transplants more than 2 years after pulmonary transplantation were acutely rejected despite maintained tolerance of the lung allografts. As a cellular control, additional animals received third-party splenocytes or donor splenocyte protein extracts. While animals treated with thirdparty splenocytes showed significant graft survival prolongation, the subcellular antigen infusion showed no such effect. In conclusion, minipigs conditioned with preoperative IRR and donor, or third-party, splenocyte infusions may develop long-term donorspecific pulmonary allograft survival in the presence of high levels of circulating regulatory T cells.
In conclusion, both porcinized and humanized mouse models of heterotopic subcutaneous bronchus transplantation imitate the in vivo development of bronchiolitis obliterans syndrome-like lesions and reveal its sensitivity to T-cell regulation.
In this study, we analyzed PRRS virus (PRRSv) specific lymphocyte function in piglets vaccinated with Ingelvac PRRSFLEX EU® at two and three weeks of age in the presence of homologous maternal immunity. Complete analysis of maternal immunity to PRRSv was evaluated postpartum, as well as passive transfer of antibodies and T cells to the piglet through colostrum intake and before and after challenge with a heterologous PRRSv at ten weeks of age. Maternal-derived antibodies were detected in piglets but declined quickly after weaning. However, vaccinated animals restored PRRSv-specific antibody levels by anamnestic response to vaccination. Cell analysis in colostrum and milk revealed presence of PRRSv-specific immune cells at suckling with higher concentrations found in colostrum than in milk. In addition, colostrum and milk contained PRRSv-specific IgA and IgG that may contribute to protection of newborn piglets. Despite the presence of PRRSv-specific Peripheral Blood Mononuclear cells (PBMCs) in colostrum and milk, no PRRSv-specific cells could be detected from blood of the piglets at one or two weeks of life. Nevertheless, cellular immunity was detectable in pre-challenged piglets up to 7 weeks after vaccination while the non-vaccinated control group showed no interferon (IFN) γ response to PRRSv stimulation. After challenge, all piglets developed a PRRSv-specific IFNγ-response, which was more robust at significantly higher levels in vaccinated animals compared to the primary response to PRRSv in non-vaccinated animals. Cytokine analysis in the lung lumen showed a reduction of pro-inflammatory responses to PRRSv challenge in vaccinated animals, especially reduced interferon (IFN) α levels. In conclusion, vaccination of maternally positive piglets at 2 and 3 weeks of age with Ingelvac PRRSFLEX EU induced a humoral and cellular immune response to PRRSv and provided protection against virulent, heterologous PRRSv challenge.
BackgroundPreoperative low-dose whole-body irradiation (IRR) with 1.5 and 7 Gy thymic IRR of the recipient, combined with a perioperative donor splenocyte infusion lead to reliable donor specific peripheral tolerance in our allogeneic porcine lung transplantation model. To reduce the toxicity of this preconditioning regime, modifications of the IRR protocol and their impact on allograft survival were assessed.MethodsLeft-sided single lung transplantation from major histocompatibility complex and sex mismatched donors was performed in 14 adult female minipigs. Recipient animals were exposed to 3 different protocols of nonmyeloablative IRR within 12 hours before transplantation. All animals were administered a donor splenocyte infusion on the day of lung transplantation. Intravenous pharmacologic immunosuppression was withdrawn after 28 postoperative days. Allograft survival was monitored by chest radiographs and bronchoscopy.ResultsIRR prolonged transplant survival in a dose- and field-dependent manner. Shielding of the bone marrow from IRR (total lymphoid IRR at 1.5 and 7 Gy thymic IRR) significantly reduced protocol toxicity defined as thrombocytopenia and consecutive increased bleeding propensity, but had a less effective impact on graft survival. Whole-body IRR at 0.5 and 7 Gy thymic IRR proved to be ineffective for reliable tolerance induction. Eventually, high levels of circulating CD4+CD25high regulatory T cells were present in long-term survivors.ConclusionsThese data show that the infusion of donor-specific alloantigen in combination with IRR is efficient once a threshold dose is exceeded.
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