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

Nanhua Chen,Jianzhong Zhu,Xiuling Yu,Zhe Sun,Xilin Yan,Ming Qiu,Shaobin Shang,Xinshuai Li,Kegong Tian,Hong Lin,Jixiang Li,Shubin Li,Shuai Li,Yunfei Tian,Yanzhao Xiao

doi:10.1186/s13567-021-00944-8

Abstract

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.

Highlights

Porcine reproductive and respiratory syndrome (PRRS) is an economically significant viral disease in the swineproducing countries of the world
The synthetic PRRSV2 ORF2-6-CON sequence was located at the center of the phylogenetic tree (Figure 1A), sharing > 90% nucleotide identities to all four lineages of PRRSV2 isolates and an increased nucleotide identity to PRRSV1 isolate (Figure 1B)
We describe the generation of a chimeric HP-PRRSV2 virus containing a consensus sequence of PRRSV2 ORF2-6 genes, which could induce broad nAbs (bnAbs) and confer cross protection against a heterologous NADC30-like PRRSV2 isolate

Summary

Introduction

Porcine reproductive and respiratory syndrome (PRRS) is an economically significant viral disease in the swineproducing countries of the world. The clinical symptoms are characterized by reproductive failure in sows and respiratory disease in young pigs [1]. In China, even though PRRSV1 isolates were sporadically detected in recent years, PRRSV2 isolates were obviously predominant [5]. In 2006, highly pathogenic PRRSV2 (HP-PRRSV2) variants first emerged in China, which were characterized by high fever (40–42 °C), high morbidity (50–100%) and high mortality (20–100%) in all ages of pigs [7]. Since 2013, NADC30-like PRRSV2 variants have become prevalent in China [8]. Since 2017, NADC34-like PRRSV2 isolates have been detected [9]. The coexistence of distinct PRRSV isolates within one pig herd or even within one pig has been identified in the field [5, 10]

Methods

Results

Conclusion