Kimman Tjeerd G, Cornelissen Lisette A, Moormann Rob J, Rebel Johanna M J, Stockhofe-Zurwieden Norbert
Central Veterinary Institute of Wageningen UR (CVI), P.O. Box 65, 8200 AB Lelystad, The Netherlands.
Vaccine. 2009 Jun 8;27(28):3704-18. doi: 10.1016/j.vaccine.2009.04.022. Epub 2009 May 3.
Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be a threat for the pig industry. Vaccines have been developed, but these failed to provide sustainable disease control, in particular against genetically unrelated strains. Here we give an overview of current knowledge and gaps in our knowledge that may be relevant for the development of a future generation of more effective vaccines. PRRSV replicates in cells of the monocyte/macrophage lineage, induces apoptosis and necrosis, interferes with the induction of a proinflammatory response, only slowly induces a specific antiviral response, and may cause persistent infections. The virus appears to use several evasion strategies to circumvent both innate and acquired immunity, including interference with antigen presentation, antibody-mediated enhancement, reduced cell surface expression of viral proteins, and shielding of neutralizing epitopes. In particular the downregulation of type I interferon-alpha production appears to interfere with the induction of acquired immunity. Current vaccines are ineffective because they suffer both from the immune evasion strategies of the virus and the antigenic heterogeneity of field strains. Future vaccines therefore must "uncouple" the immune evasion and apoptogenic/necrotic properties of the virus from its immunogenic properties, and they should induce a broad immune response covering the plasticity of its major antigenic sites. Alternatively, the composition of the vaccine should be changed regularly to reflect presently and locally circulating strains. Preferably new vaccines should also allow discriminating infected from vaccinated pigs to support a virus elimination strategy. Challenges in vaccine development are the incompletely known mechanisms of immune evasion and immunity, lack of knowledge of viral sequences that are responsible for the pathogenic and immunosuppressive properties of the virus, lack of knowledge of the forces that drive antigenic heterogeneity and its consequences for immunogenicity, and a viral genome that is relatively intolerant for subtle changes at functional sites.
猪繁殖与呼吸综合征病毒（PRRSV）仍然是养猪业面临的一大威胁。疫苗虽已研发出来，但这些疫苗未能实现可持续的疾病防控，尤其是针对基因不相关的毒株。在此，我们概述了当前的知识以及知识空白，这些可能与下一代更有效疫苗的研发相关。PRRSV在单核细胞/巨噬细胞谱系的细胞中复制，诱导细胞凋亡和坏死，干扰促炎反应的诱导，仅缓慢诱导特异性抗病毒反应，并可能导致持续性感染。该病毒似乎采用多种逃避策略来规避先天免疫和获得性免疫，包括干扰抗原呈递、抗体介导的增强作用、病毒蛋白细胞表面表达的减少以及中和表位的屏蔽。特别是I型干扰素-α产生的下调似乎干扰了获得性免疫的诱导。当前的疫苗无效，因为它们既受到病毒免疫逃避策略的影响，又受到田间毒株抗原异质性的影响。因此，未来的疫苗必须将病毒的免疫逃避和凋亡/坏死特性与其免疫原性“脱钩”，并且应诱导广泛的免疫反应，覆盖其主要抗原位点的可塑性。或者，应定期改变疫苗的组成，以反映当前和当地流行的毒株。理想情况下，新疫苗还应能够区分感染猪和接种疫苗的猪，以支持病毒消除策略。疫苗研发面临的挑战包括免疫逃避和免疫机制尚不完全清楚、对负责病毒致病性和免疫抑制特性的病毒序列缺乏了解、对驱动抗原异质性的因素及其对免疫原性的影响缺乏了解，以及病毒基因组对功能位点的细微变化相对不耐受。
