Chimeric HP-PRRSV2 containing an ORF2-6 consensus sequence induces antibodies with broadly neutralizing activity and confers cross protection against virulent NADC30-like isolate

Veterinary Research

Ming Qiu¹  Shuai Li¹  Yanzhao Xiao¹  Xilin Yan¹  Xinshuai Li¹  Hong Lin¹  Shubin Li¹  Yunfei Tian¹  Jixiang Li¹  Nanhua Chen²  Shaobin Shang²  Jianzhong Zhu²  Zhe Sun³  Xiuling Yu³  Kegong Tian³ 

[1] College of Veterinary Medicine, Yangzhou University, 225009, Yangzhou, Jiangsu, China;College of Veterinary Medicine, Yangzhou University, 225009, Yangzhou, Jiangsu, China;Joint International Research Laboratory of Agriculture and Agri-Product Safety, 225009, Yangzhou, Jiangsu, China;Comparative Medicine Research Institute, Yangzhou University, 225009, Yangzhou, Jiangsu, China;Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, 225009, Yangzhou, China;National Research Center for Veterinary Medicine, 471003, Luoyang, Henan, China;

关键词: PRRSV;    Infectious clone;    ORF2-6 consensus sequence;    Broadly neutralizing antibodies;    Cross protection;    Genetic engineered vaccine;   

DOI  :  10.1186/s13567-021-00944-8

来源: Springer

【 摘 要 】

Due to the substantial genetic diversity of porcine reproductive and respiratory syndrome virus (PRRSV), commercial PRRS vaccines fail to provide sufficient cross protection. Previous studies have confirmed the existence of PRRSV broadly neutralizing antibodies (bnAbs). However, bnAbs are rarely induced by either natural infection or vaccination. In this study, we designed and synthesized a consensus sequence of PRRSV2 ORF2-6 genes (ORF2-6-CON) encoding all envelope proteins based on 30 representative Chinese PRRSV isolates. The ORF2-6-CON sequence shared > 90% nucleotide identities to all four lineages of PRRSV2 isolates in China. A chimeric virus (rJS-ORF2-6-CON) containing the ORF2-6-CON was generated using the avirulent HP-PRRSV2 JSTZ1712-12 infectious clone as a backbone. The rJS-ORF2-6-CON has similar replication efficiency as the backbone virus in vitro. Furthermore, pig inoculation and challenge studies showed that rJS-ORF2-6-CON is not pathogenic to piglets and confers better cross protection against the virulent NADC30-like isolate than a commercial HP-PRRS modified live virus (MLV) vaccine. Noticeably, the rJS-ORF2-6-CON strain could induce bnAbs while the MLV strain only induced homologous nAbs. In addition, the lineages of VDJ repertoires potentially associated with distinct nAbs were also characterized. Overall, our results demonstrate that rJS-ORF2-6-CON is a promising candidate for the development of a PRRS genetic engineered vaccine conferring cross protection.

【 授权许可】

CC BY