Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Avda. Puerta de Hierro s/n, 28040 Madrid, Spain.
Vaccine. 2011 Sep 16;29(40):6928-40. doi: 10.1016/j.vaccine.2011.07.076. Epub 2011 Jul 30.
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is highly heterogenic. This heterogeneity has an effect on antigenic composition of PRRSV and might create differences in sensitivity to neutralization between isolates. The sensitivity to neutralization could be an important feature of PRRSV isolates because it is likely that isolates resistant to neutralization pose a significant challenge for the development of vaccines that elicit broad protective immunity. Nonetheless, little information is available for understanding or categorizing the viral neutralization phenotype of PRRSV isolates. Consequently, the main purpose of this study was to determine whether PRRSV isolates differ in their susceptibility to neutralization and if they can be classified in different categories based on their neutralization phenotype. For this purpose, a panel of 39 PRRSV isolates and a set of 30 hyperimmune monospecific sera were used in cross-neutralization assays. The results of this study indicate that PRRSV isolates differ in their sensitivity to neutralization and k-means clustering system allowed classifying the isolates in four different categories according to their neutralization phenotype: highly sensitive, sensitive, moderately sensitive and resistant to neutralization. Further analyses using two additional clustering systems that considered individual data for the classification of the isolates confirmed that classification obtained by k-means is accurate in most cases and that only in a few instances classification is less stringent. Sequences of GP3, GP4 and GP5 were analyzed but no correlation could be found between the sequence of previously identified neutralizing epitopes or the number of N-linked glycosylation sites in different proteins and the neutralization phenotype of the isolates. These data provide the first systematic assessment of overall neutralization sensitivities of a panel of diverse PRRSV isolates. The classification of the isolates provides a useful tool to facilitate the systematic characterization of neutralizing antibody production elicited by new vaccine candidates.
猪繁殖与呼吸综合征病毒（PRRSV）高度异质。这种异质性影响 PRRSV 的抗原组成，并可能导致分离株之间的中和敏感性存在差异。分离株的中和敏感性可能是 PRRSV 的一个重要特征，因为对中和具有抗性的分离株可能对开发能够引发广泛保护免疫的疫苗构成重大挑战。尽管如此，对于理解或分类 PRRSV 分离株的病毒中和表型，我们所掌握的信息仍然很少。因此，本研究的主要目的是确定 PRRSV 分离株在中和敏感性方面是否存在差异，以及它们是否可以根据其中和表型分为不同类别。为此，本研究使用了 39 个 PRRSV 分离株和 30 种单特异性高免血清的组合进行交叉中和测定。研究结果表明，PRRSV 分离株在中和敏感性方面存在差异，并且使用 K-均值聚类系统可以根据其中和表型将分离株分为四个不同类别：高度敏感、敏感、中度敏感和对中和具有抗性。使用另外两种聚类系统对分类进行进一步分析，这些系统考虑了分类分离株的个体数据，进一步证实了 K-均值聚类系统的分类在大多数情况下是准确的，只有在少数情况下分类不太严格。还分析了 GP3、GP4 和 GP5 的序列，但未发现先前鉴定的中和表位序列或不同蛋白中 N-连接糖基化位点的数量与分离株的中和表型之间存在相关性。这些数据首次对一组不同 PRRSV 分离株的总体中和敏感性进行了系统评估。分离株的分类为新疫苗候选物诱导的中和抗体产生的系统表征提供了有用的工具。
