Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China; Scientific Observing and Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, Yangling, Shaanxi, China.
Key Laboratory of Antibody Technique of National Health and Family Planning Commission, Nanjing Medical University, Nanjing, China; Department of Infectious Diseases, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Antiviral Res. 2020 Mar;175:104716. doi: 10.1016/j.antiviral.2020.104716. Epub 2020 Jan 23.
Porcine reproductive and respiratory syndrome (PRRS) is the most economically important infectious disease affecting the global swine industry, especially since vaccination has had limited impact on PRRSV prevention and control. In this study, the monoclonal antibody PR5nf1 (Mab-PR5nf1, IgM isotype) was shown to react with heterogeneous PRRSV isolates belonging to both PRRSV-1 and PRRSV-2 species. Pepsin digestion of Mab-PR5nf1 did not affect Mab binding to virions, as F(ab) fragments demonstrated the same reactivity as undigested Mab. Upon further investigation, Mab-PR5nf1 could neutralize all tested PRRSV isolates of both PRRSV-1 and PRRSV-2, suggesting it was a broadly neutralizing Mab against PRRSV. Interestingly, Mab-PR5nf1 appeared to recognize a specific virus epitope that required post-translational modification within the host cellular Golgi apparatus. Deglycosylation of PRRSV virions with PNGase F abolished Mab binding, suggesting that a novel Mab-binding epitope may exist that confers cross-protection against isolates of both PRRSV species. Additionally, immunization of mice with a cocktail of inactivated PRRSV virus and Mab-PR5nf1 enhanced cell-mediated immunity, as determined by IFN-γ ELIspot. In conclusion, this is the first report describing a novel Mab that recognizes a conserved epitope common to both PRRSV-1 and PRRSV-2 and provides valuable insights to guide future PRRSV vaccine development.
猪繁殖与呼吸综合征（PRRS）是影响全球养猪业的最重要的传染性疾病之一，尤其是疫苗对 PRRSV 的预防和控制效果有限。在这项研究中，单克隆抗体 PR5nf1（Mab-PR5nf1，IgM 同型）被证明可以与属于 PRRSV-1 和 PRRSV-2 两种病毒的异质 PRRSV 分离株发生反应。胃蛋白酶消化 Mab-PR5nf1 不会影响 Mab 与病毒粒子的结合，因为 F(ab') 片段表现出与未消化的 Mab 相同的反应性。进一步研究表明，Mab-PR5nf1 可以中和所有测试的 PRRSV-1 和 PRRSV-2 分离株，表明它是一种广谱中和针对 PRRSV 的 Mab。有趣的是，Mab-PR5nf1 似乎识别出一种特定的病毒表位，该表位需要宿主细胞高尔基体中的翻译后修饰。用 PNGase F 对 PRRSV 病毒进行去糖基化会使 Mab 结合丧失，这表明可能存在一个新的 Mab 结合表位，可以赋予针对两种 PRRSV 分离株的交叉保护作用。此外，用灭活的 PRRSV 病毒和 Mab-PR5nf1 混合物免疫小鼠增强了细胞介导的免疫，这通过 IFN-γ ELIspot 来确定。总之，这是首次报道描述一种可以识别 PRRSV-1 和 PRRSV-2 共有的保守表位的新型 Mab，并为指导未来 PRRSV 疫苗的开发提供了有价值的见解。
