Prevention and Control of Porcine Epidemic Diarrhea: The Development of Recombination-Resistant Live Attenuated Vaccines

Abstract

Porcine epidemic diarrhea (PED), causing up to 100% mortality in neonatal pigs, is a highly contagious enteric disease caused by PED virus (PEDV). The highly virulent genogroup 2 (G2) PEDV emerged in 2010 and has caused huge economic losses to the pork industry globally. It was first reported in the US in 2013, caused country-wide outbreaks, and posed tremendous hardship for many pork producers in 2013-2014. Vaccination of pregnant sows/gilts with live attenuated vaccines (LAVs) is the most effective strategy to induce lactogenic immunity in the sows/gilts and provide a passive protection via the colostrum and milk to suckling piglets against PED. However, there are still no safe and effective vaccines available after about one decade of endeavor. One of the biggest concerns is the potential reversion to virulence of an LAV in the field. In this review, we summarize the status and the major obstacles in PEDV LAV development. We also discuss the function of the transcriptional regulatory sequences in PEDV transcription, contributing to recombination, and possible strategies to prevent the reversion of LAVs. This article provides insights into the rational design of a promising LAV without safety issues.

Keywords: live attenuated vaccines; porcine epidemic diarrhea virus; recombination; safety issue.

Figure 1

The genomic organization of a PEDV and its structural (S, E, M, and N), non-structural (nsp1–16), and accessory (ORF3) proteins. The green and red bars located at the 5′ UTR or upstream of each ORF represent the leader TRS and body TRS regions. Abbreviations: a number for pp1a and pp1ab indicate the non-structural proteins 1–16. PLpro: Papain-like protease; 3CLpro: chymotrypsin-like protease; RdRp: RNA-dependent RNA polymerase; ExoN: Exoribonuclease; N7-MTase: N7-methyltransferase; EndoU: endoribonuclease; 2′-O-MTase: 2′-O methyltransferase; S: spike; E: envelop; M: membrane; and N: nucleocapsid.

Figure 2

A discontinued replication model for PEDV. When RTC encounters TRS region, it will either “read through” or “template switch” to generate discontinued sgRNAs. Modified from Baker, S.C., 2008 [62].

Figure 3

Secondary structures for the 5′ UTR of the prototype PEDV CV777 strain. Four conserved stem-loops (SLs) are predicted using Mfold [http://www.unafold.org/mfold/applications/rna-folding-form.php (accessed on 26 May 2022)], and Gibbs free energy for each SL was calculated and presented in kcal/mol.