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T cell epitope content comparison (EpiCC) analysis demonstrates a bivalent PCV2 vaccine has greater T cell epitope overlap with field strains than monovalent PCV2 vaccines.
Veterinary Immunology and Immunopathology ( IF 1.4 ) Pub Date : 2020-03-06 , DOI: 10.1016/j.vetimm.2020.110034
Meggan Bandrick 1 , Andres H Gutiérrez 2 , Prerak Desai 1 , Gonzalo Rincon 1 , William D Martin 2 , Frances E Terry 2 , Anne S De Groot 3 , Dennis L Foss 1
Affiliation  

Porcine circovirus type 2 (PCV2) has one of the highest evolutionary rates among DNA viruses. Traditionally, PCV2 vaccines have been based on the 2a genotype as this was the first genotype discovered. Today, eight genotypes of PCV2 viruses have been identified, and, taken together with the rapid evolutionary rate, propensity to recombine, and high rate of vaccination, further variation in PCV2 is expected. For these reasons, there is a growing genetic gap between available vaccines and field strains. When selecting vaccines, it is important to consider vaccines that contain T cell epitopes that are well-matched to the circulating strains. To quantify the relatedness between PCV2 vaccines and field strains, we predicted and compared their T cell epitope content and calculated Epitope Content Comparison (EpiCC) scores using established in silico tools. T cell epitopes predicted to bind common class I and class II swine leukocyte antigen (SLA) alleles were identified from two major structural proteins, the capsid (encoded by ORF2) and the replicase (encoded by ORF1). The T cell epitope content of three commercial PCV2a-based vaccines (a baculovirus expressed PCV2a ORF2 [VacAlt], a PCV1-PCV2a chimeric virus vaccine [VacA] and a combination cPCV2a-cPCV2b chimeric virus vaccine [VacAB]) and an experimental PCV2b ORF2-based chimeric virus vaccine [VacB] (Table 1), were compared to that of 161 PCV2 field strains (representing genotypes a-f). The T cell epitope content and conservation between vaccine and field strains varied. While all vaccine strains provided broad coverage of the field strains including heterologous genotypes, none of the vaccines covered all the putative T cell epitopes identified in the field strains. PCV2a-based vaccine strains generally scored higher in terms of conserved epitope content against PCV2a field isolates but were not identical. The PCV2b-based vaccine strain had higher scores against PCV2b and PCV2d field strains. The combination PCV2a-PCV2b vaccine (VacAB) had, on average, the highest EpiCC score. PCV2 continues to evolve and EpiCC analysis provides a new tool to assess the possible impact of virus genetic divergence on T cell epitope coverage of vaccine strains. Given that multiple genotypes are currently found and may co-exist on farms, this analysis suggests that a combination of PCV2a and PCV2b vaccine strains may be required to provide optimal coverage of current and future field isolates.

中文翻译:

T细胞表位含量比较(EpiCC)分析表明,与一价PCV2疫苗相比,二价PCV2疫苗与田间毒株的T细胞表位重叠更大。

猪圆环病毒2型(PCV2)在DNA病毒中具有最高的进化速率之一。传统上,PCV2疫苗基于2a基因型,因为这是第一个发现的基因型。如今,已鉴定出八种PCV2病毒基因型,并结合快速的进化速度,重组倾向和高疫苗接种率,预计PCV2会进一步发生变异。由于这些原因,可用的疫苗和田间毒株之间的遗传差距越来越大。在选择疫苗时,重要的是要考虑含有与循环中的毒株完全匹配的T细胞表位的疫苗。为了量化PCV2疫苗与野毒株之间的相关性,我们预测并比较了它们的T细胞表位含量,并使用已建立的计算机工具计算了表位含量比较(EpiCC)得分。从两个主要的结构蛋白,衣壳(由ORF2编码)和复制酶(由ORF1编码)中鉴定出预计会结合常见的I类和II类猪白细胞抗原(SLA)等位基因的T细胞表位。三种商业PCV2a疫苗(表达杆状病毒的PCV2a ORF2 [VacAlt],PCV1-PCV2a嵌合病毒疫苗[VacA]和组合cPCV2a-cPCV2b嵌合病毒疫苗[VacAB])和实验PCV2b ORF2的T细胞表位含量的嵌合病毒疫苗[VacB](表1)与161种PCV2野毒株(代表af型)进行了比较。疫苗和田间毒株之间的T细胞表位含量和保守性有所不同。尽管所有疫苗菌株都广泛覆盖了包括异源基因型在内的田间菌株,但没有一种疫苗能覆盖田间菌株中鉴定出的所有假定的T细胞表位。基于PCV2a的疫苗株相对于PCV2a野外分离株保守的抗原决定簇含量通常得分较高,但并不完全相同。基于PCV2b的疫苗株对PCV2b和PCV2d田间株的评分更高。平均而言,组合PCV2a-PCV2b疫苗(VacAB)的EpiCC得分最高。PCV2继续发展,EpiCC分析提供了一种新工具,可评估病毒遗传差异对疫苗株T细胞表位覆盖率的可能影响。鉴于目前有多种基因型可以在农场中共存,
更新日期:2020-03-06
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