Isolation and Identification of a Recombinant Porcine Epidemic Diarrhea Virus With a Novel Insertion in S1 Domain

Porcine epidemic diarrhea virus (PEDV) causes devastating enteric disease that inflicts huge economic damage on the swine industry worldwide. A safe and highly effective PEDV vaccine that contains only the virus-neutralizing epitopes (not enhancing epitope), as well as a ready-to-use PEDV neutralizing antibody for the passive immunization of PEDV vulnerable piglets (during the first week of life) are needed, particularly for PEDV-endemic farms. In this study, we generated monoclonal antibodies (mAbs) to the recombinant S1 domain of PEDV spike (S) protein and tested their PEDV neutralizing activity by CPE-reduction assay. The mAb secreted by one hybrodoma clone (A3), that also bound to the native S1 counterpart from PEDV-infected cells (tested by combined co-immunoprecipitation and Western blotting), neutralized PEDV infectivity. Epitope of the neutralizing mAb (mAbA3) locates in the S1A subdomain of the spike protein, as identified by phage mimotope search and multiple sequence alignment, and peptide binding-ELISA. The newly identified epitope is shared by PEDV G1 and G2 strains and other alphacoronaviruses. In summary, mAbA3 may be useful as a ready-to-use antibody for passive immunization of PEDV-susceptible piglets, while the novel neutralizing epitope, together with other, previously known protective epitopes, have potential as an immunogenic cocktail for a safe, next-generation PEDV vaccine.

Section: Supplementary Materialsmentioning

confidence: 99%

Novel Neutralizing Epitope of PEDV S1 Protein Identified by IgM Monoclonal Antibody

Thavorasak

Chulanetra

Glab-ampai

et al. 2022

“…PEDV strains can be sorted into two genogroups, GI (classical) and GII (variant). Each genogroup can then be divided into two sub-groups, GI-a, GI-b, GII-a, and GII-b [5,6,9,30]. The rate of PEDV strain belonging to GII genogroup has been revealed to escalate in China between 2011 to 2018 and the strains of the GII-b sub-group seemed to gradually occupy a dominant position [5,22,31,32].…”

Section: Discussionmentioning

confidence: 99%

Levistolide A Inhibits PEDV Replication via Inducing ROS Generation

Zeng

Ren

et al. 2022

Porcine epidemic diarrhea virus (PEDV) variant strains adversely affect the production of pigs globally. Vaccines derived from PEDV traditional strains impart less protection against the variant strains. Moreover, sequence diversity among different PEDV variant strains is also complicated. This necessitates developing alternative antiviral strategies for defending against PEDV. This study explored a natural product, Levistolide A (LA), to possess antiviral activity against PEDV. LA was found to suppress PEDV replication in a dose-dependent manner. And the inhibitory effect of LA against PEDV was maintained in the course of time. In terms of viral RNA and protein production, LA also showed a strong inhibitory effect. In addition, LA was indicated to inhibit PEDV from attaching to the cellular membrane or penetrating the cells. Further study revealed that LA can induce the generation of reactive oxygen species (ROS), and the corresponding inhibitor, NAC, was found to antagonize the effect of LA on inhibiting PEDV replication. This illustrated that the LA-induced ROS generation played an important role in its anti-PEDV activity. LA was also identified to stimulate ER stress, which is an important consequence of ROS production and was proven to be able to inhibit PEDV replication. To conclude, this study revealed that LA can inhibit PEDV replication via inducing ROS generation.

“…Vaccine failures caused by recombination-driven reversion occurred for several LAVs for animal viruses, including canine parvovirus [113], infectious bursal disease virus [114], bovine herpesvirus 1 [115], as well as members from CoVs, IBV [116], and PEDV [117]. PEDV-recombinant variants were observed from several major pigfarming provinces in China [117][118][119]. One variant exhibiting high pathogenicity in the field was derived from a recombination event between low-pathogenic vaccine and virulent field strains [117].…”

Section: Risk and Prevention Of Virulence Reversion Of Pedv Live Atte...mentioning

confidence: 99%

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

Niu

Wang

2022

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.