Robinson Sally R, Li Juan, Nelson Eric A, Murtaugh Michael P
Department of Veterinary and Biomedical Sciences, University of Minnesota, 1971 Commonwealth Avenue, St. Paul, MN 55108, USA.
Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA.
Virus Res. 2015 May 4;203:56-65. doi: 10.1016/j.virusres.2015.03.016. Epub 2015 Apr 4.
Neutralizing antibodies are a critical part of the immune armory for defense against viruses, and the mechanism by which many effective vaccines work to protect against viral infections. However, infections by rapidly evolving and genetically diverse viruses are often characterized by ineffective neutralizing antibody responses. Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly genetically diverse RNA virus that causes PRRS, the most significant disease of pigs worldwide. The prevailing view of immunity to PRRSV is characterized by delayed and ineffectual production of neutralizing antibodies lacking cross-reactivity that is necessary for vaccine efficacy. Using an ELISA-based neutralizing assay developed to analyze PRRSV growth in porcine alveolar macrophages, the naturally permissive cell of PRRSV, we showed that sera from previously infected commercial sows had high levels of neutralizing activity against diverse PRRSV strains, including across distinct genotypes of PRRSV. Fifty percent cross-neutralization titers in excess of 1/1024 were observed. Neutralizing activity was dose-dependent and was maintained in the immunoglobulin fraction. Presence of high-titer, anti-PRRSV antibody activity that cross-neutralizes diverse strains of virus has prompted reevaluation of the role of neutralizing antibodies for cross-protection against PRRSV under field conditions. Understanding conditions that favor development of cross-neutralizing activity will be crucial for improved strategies to enhance cross-protection against PRRSV. More detailed studies are expected to elucidate mechanisms of neutralizing antibody production and maturation and to investigate conserved epitope targets of cross-neutralization in this rapidly evolving virus.
中和抗体是抵御病毒的免疫武器库的关键组成部分，也是许多有效疫苗预防病毒感染的作用机制。然而，被快速进化且基因多样的病毒感染时，往往表现为中和抗体反应无效。猪繁殖与呼吸综合征病毒（PRRSV）是一种基因高度多样的RNA病毒，可引发猪繁殖与呼吸综合征，这是全球养猪业中最严重的疾病。目前关于对PRRSV免疫的普遍观点是，中和抗体产生延迟且无效，缺乏疫苗效力所需的交叉反应性。我们利用一种基于酶联免疫吸附测定（ELISA）开发的中和试验来分析PRRSV在其天然易感细胞——猪肺泡巨噬细胞中的生长情况，结果显示，先前感染过的商业母猪的血清对多种PRRSV毒株具有高水平的中和活性，包括不同基因型的PRRSV。观察到50%交叉中和效价超过1/1024。中和活性呈剂量依赖性，并在免疫球蛋白组分中得以维持。存在能交叉中和多种病毒毒株的高滴度抗PRRSV抗体活性，这促使人们重新评估中和抗体在田间条件下对PRRSV交叉保护中的作用。了解有利于交叉中和活性发展的条件对于改进增强对PRRSV交叉保护的策略至关重要。预计更详细的研究将阐明中和抗体产生和成熟的机制，并研究这种快速进化病毒中交叉中和的保守表位靶点。
