PMID- 34044890 OWN - NLM STAT- MEDLINE DCOM- 20210907 LR - 20210907 IS - 1297-9716 (Electronic) IS - 0928-4249 (Print) IS - 0928-4249 (Linking) VI - 52 IP - 1 DP - 2021 May 27 TI - Chimeric HP-PRRSV2 containing an ORF2-6 consensus sequence induces antibodies with broadly neutralizing activity and confers cross protection against virulent NADC30-like isolate. PG - 74 LID - 10.1186/s13567-021-00944-8 [doi] LID - 74 AB - 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. FAU - Chen, Nanhua AU - Chen N AUID- ORCID: 0000-0002-1909-8760 AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China. chnhlh@126.com. AD - Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou, 225009, Jiangsu, China. chnhlh@126.com. AD - Comparative Medicine Research Institute, Yangzhou University, Yangzhou, 225009, Jiangsu, China. chnhlh@126.com. AD - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, China. chnhlh@126.com. FAU - Li, Shubin AU - Li S AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China. FAU - Tian, Yunfei AU - Tian Y AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China. FAU - Li, Xinshuai AU - Li X AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China. FAU - Li, Shuai AU - Li S AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China. FAU - Li, Jixiang AU - Li J AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China. FAU - Qiu, Ming AU - Qiu M AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China. FAU - Sun, Zhe AU - Sun Z AD - National Research Center for Veterinary Medicine, Luoyang, 471003, Henan, China. FAU - Xiao, Yanzhao AU - Xiao Y AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China. FAU - Yan, Xilin AU - Yan X AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China. FAU - Lin, Hong AU - Lin H AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China. FAU - Yu, Xiuling AU - Yu X AD - National Research Center for Veterinary Medicine, Luoyang, 471003, Henan, China. FAU - Tian, Kegong AU - Tian K AD - National Research Center for Veterinary Medicine, Luoyang, 471003, Henan, China. FAU - Shang, Shaobin AU - Shang S AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China. shaobinshang@yzu.edu.cn. AD - Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou, 225009, Jiangsu, China. shaobinshang@yzu.edu.cn. AD - Comparative Medicine Research Institute, Yangzhou University, Yangzhou, 225009, Jiangsu, China. shaobinshang@yzu.edu.cn. AD - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, China. shaobinshang@yzu.edu.cn. FAU - Zhu, Jianzhong AU - Zhu J AD - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China. jzzhu@yzu.edu.cn. AD - Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou, 225009, Jiangsu, China. jzzhu@yzu.edu.cn. AD - Comparative Medicine Research Institute, Yangzhou University, Yangzhou, 225009, Jiangsu, China. jzzhu@yzu.edu.cn. AD - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, China. jzzhu@yzu.edu.cn. LA - eng GR - 31802172/National Natural Science Foundation of China/ GR - BK20170492/Natural Science Foundation of Jiangsu Province/ PT - Journal Article DEP - 20210527 PL - England TA - Vet Res JT - Veterinary research JID - 9309551 RN - 0 (Broadly Neutralizing Antibodies) SB - IM MH - Animals MH - Broadly Neutralizing Antibodies/genetics/*immunology MH - Consensus Sequence MH - Cross Protection/*immunology MH - *Open Reading Frames MH - Porcine Reproductive and Respiratory Syndrome/*immunology MH - Porcine respiratory and reproductive syndrome virus/genetics/*immunology/pathogenicity MH - Sus scrofa MH - Swine MH - Virulence PMC - PMC8161975 OTO - NOTNLM OT - Broadly neutralizing antibodies OT - Cross protection OT - Genetic engineered vaccine OT - Infectious clone OT - ORF2-6 consensus sequence OT - PRRSV COIS- The authors declare that they have no competing interests. EDAT- 2021/05/29 06:00 MHDA- 2021/09/08 06:00 PMCR- 2021/05/27 CRDT- 2021/05/28 06:16 PHST- 2021/01/12 00:00 [received] PHST- 2021/04/03 00:00 [accepted] PHST- 2021/05/28 06:16 [entrez] PHST- 2021/05/29 06:00 [pubmed] PHST- 2021/09/08 06:00 [medline] PHST- 2021/05/27 00:00 [pmc-release] AID - 10.1186/s13567-021-00944-8 [pii] AID - 944 [pii] AID - 10.1186/s13567-021-00944-8 [doi] PST - epublish SO - Vet Res. 2021 May 27;52(1):74. doi: 10.1186/s13567-021-00944-8.