Li Jixiang, Li Shubin, Qiu Ming, Li Xinshuai, Li Chen, Feng Binghui, Lin Hong, Zheng Wanglong, Zhu Jianzhong, Chen Nanhua
College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China.
College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratories of Agriculture and Agri-Product Safety, Yangzhou, Jiangsu 225009, China; Comparative Medicine Research Institute, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
Virus Res. 2022 Jul 2;315:198789. doi: 10.1016/j.virusres.2022.198789. Epub 2022 Apr 26.
High genetic diversity of porcine reproductive and respiratory syndrome virus (PRRSV) isolates is a major obstacle for the development of effective PRRS vaccines. A chimeric highly pathogenic PRRSV2 (HP-PRRSV2) strain containing the consensus sequence of ORF2-6 genes was constructed in our previous study, which could induce broadly neutralizing antibodies (bnAbs) and confer satisfied cross protection against virulent NADC30-like isolate. To further elucidate the roles of minor and major envelope proteins encoded by ORF2-4 and ORF5-6 genes in conferring cross protection, two chimeric HP-PRRSV2 strains (rJS-ORF2-4-CON and rJS-ORF5-6-CON) containing consensus sequences of ORF2-4 or ORF5-6 were constructed and rescued in this study. The rJS-ORF5-6-CON strain has similar replication efficiency as the backbone HP-PRRSV2 rJSTZ1712-12 virus, while rJS-ORF2-4-CON has significantly lower in vitro and in vivo replication efficiency comparing to rJS-ORF5-6-CON. Animal inoculation indicated that both rJS-ORF2-4-CON and rJS-ORF5-6-CON did not cause obvious clinical signs in piglets and could induce heterologous nAbs after immunization. Challenge with a virulent heterologous NADC30-like SD17-38 isolate showed that even though both immunized groups presented lower viremia, faster virus elimination, less fever and alleviated lung gross lesions when compared with the only challenged pigs, rJS-ORF2-4-CON and rJS-ORF5-6-CON could not confer enough cross protection. Considering the bnAbs and satisfied cross protection induced by the chimeric virus containing ORF2-6 consensus sequence, our results support that minor and major envelope proteins play synergistic roles in inducing broader nAbs and conferring better cross protection.
猪繁殖与呼吸综合征病毒（PRRSV）分离株的高遗传多样性是有效PRRS疫苗研发的主要障碍。在我们之前的研究中构建了一种嵌合的高致病性PRRSV2（HP-PRRSV2）毒株，其包含ORF2 - 6基因的共有序列，该毒株可诱导广泛中和抗体（bnAbs）并对强毒NADC30样分离株提供满意的交叉保护。为了进一步阐明由ORF2 - 4和ORF5 - 6基因编码的次要和主要包膜蛋白在提供交叉保护中的作用，本研究构建并拯救了两种包含ORF2 - 4或ORF5 - 6共有序列的嵌合HP-PRRSV2毒株（rJS-ORF2 - 4-CON和rJS-ORF5 - 6-CON）。rJS-ORF5 - 6-CON毒株的复制效率与亲本HP-PRRSV2 rJSTZ1712-12病毒相似，而rJS-ORF2 - 4-CON在体外和体内的复制效率与rJS-ORF5 - 6-CON相比显著更低。动物接种表明，rJS-ORF2 - 4-CON和rJS-ORF5 - 6-CON在仔猪中均未引起明显临床症状，免疫后均可诱导异源中和抗体（nAbs）。用强毒异源NADC30样SD17-38分离株进行攻毒试验表明，尽管与仅攻毒的猪相比，两个免疫组均表现出较低的病毒血症、更快的病毒清除、更低的发热以及减轻的肺部肉眼病变，但rJS-ORF2 - 4-CON和rJS-ORF5 - 6-CON不能提供足够的交叉保护。考虑到含有ORF2 - 6共有序列的嵌合病毒诱导的bnAbs和满意的交叉保护，我们的结果支持次要和主要包膜蛋白在诱导更广泛的nAbs和提供更好的交叉保护中发挥协同作用。
