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Classical swine fever virus (CSFV; the Jeju LOM strain) and other pathogens detected in pigs (2014-2018).
Source publication
Here, we examine the effects of LOM(Low virulence of Miyagi) strains isolated from pigs (Jeju LOM strains) of Jeju Island, where vaccination with a live attenuated classical swine fever (CSF) LOM vaccine strain was stopped. The circulation of the Jeju LOM strains was mainly caused by a commercial swine erysipelas (Erysipelothrix rhusiopathiae) vacc...
Contexts in source publication
Context 1
... derived from the Jeju LOM strain were detected in tissue samples from 51 suckling piglets, 14 piglets were infected with Jeju LOM alone, and the remaining 37 were co-infected with Jeju LOM plus enteric pathogens (six with Clostridium spp, six with E. coli, three with PEDV, and four with rotavirus), respiratory pathogens (three with PRRSV), or Streptococcus (n = 7), and Staphylococcus spp. (n = 2) ( Table 1). Samples from the 37 suckling piglets co-infected with the Jeju LOM strain and other pathogens showed evidence of interior visceral hemorrhage (18 of the kidney, 12 of the exo-endocardium, and nine of the lung), and 14 had non-purulent brain lesions (perivascular cuffing, gliosis, and neuronophagia). ...Context 2
... of the 14 suckling piglets identified to have CSF-like specific histopathologic lesions (Figure 1). Pathogenic lesions in weaning pigs included broncho-interstitial pneumonia or fibrinous lobor pneumonia (n = 16), lung hemorrhage (n = 10), kidney hemorrhage (n = 9), peripheral lymph node hemorrhage (n = 11), exo-endocardium hemorrhage (n = 5), and nonsuppurative encephalitis of brain and spinal cord (n = 5) ( Table 1). Co-infection of 22 fetuses with other pathogens (i.e., PPV, ADV, EMCV, JEV, PRRSV, and PCV2) was not confirmed, and no specific pathogenic lesions were observed in their organs. ...Context 3
... amino acid sequences of four commercial LOM vaccine strains were compared with those of five Jeju LOM strains (2004)(2005)(2006)(2007), and three unique amino acid changes in the E1 (V-577-A/M) and NS4B (M-2378L and V-2383A) proteins were detected (Supplemental Table S1). Comparison of the Jeju LOM strain JJ04LOM-Tamra01 (2004) with the four other Jeju LOM strains (2005)(2006)(2007) revealed six amino acid changes: E rns (D-386-N, R-480-G), E2 (L-1065-S), NS3 (K-1165-R), NS4B (A-2352-V), and NS5A (N-2816-T) (Supplemental Table S1 Table 2). ...Context 4
... amino acid sequences of four commercial LOM vaccine strains were compared with those of five Jeju LOM strains (2004)(2005)(2006)(2007), and three unique amino acid changes in the E1 (V-577-A/M) and NS4B (M-2378L and V-2383A) proteins were detected (Supplemental Table S1). Comparison of the Jeju LOM strain JJ04LOM-Tamra01 (2004) with the four other Jeju LOM strains (2005)(2006)(2007) revealed six amino acid changes: E rns (D-386-N, R-480-G), E2 (L-1065-S), NS3 (K-1165-R), NS4B (A-2352-V), and NS5A (N-2816-T) (Supplemental Table S1 Table 2). ...Context 5
... Materials: The following are available online at www.mdpi.com/2076-0817/8/4/251/s1. Amino acid differences between commercial LOM vaccine strains and Jeju LOM strains (2004)(2005)(2006)(2007), Table S1: (https://zenodo.org/deposit/3484007) and (2014)(2015)(2016)(2017)(2018), Author Contributions: I.-S.C., B.-H.H., B.-K.P. and D-.J.A. conceived the study; S.C., J.-H.K. and D.-.J.A. designed the experiments; S.C., J.-H.K., K.-S.K., S.S., W.-C.K., H.-J.K., G.-N.P. and R.-M.C. performed the experiments; J.-H.K., W.-C.K. and H.-J.K. acquired samples; S.C., R.-M.C. and D.-J.A. drafted the manuscript. ...Citations
... Moreover, there has been an uncertainty regarding a potential reversion of LAM-LOM to virulence, although it has been considered genetically stable through continuous propagation in bovine or porcine kidney cells. In fact, the unintentional vaccination of LAV-LOM in CSFV-naïve sow herds in 2014 resulted in the reemergence of CSFV in Jeju province, the largest island of South Korea, which had achieved a CSF-free status and then prohibited prophylactic vaccination in 1998 [17][18][19]. Subsequent animal studies have revealed clinical adverse effects of the used LAV-LOM in pigs [17,20]. Since its reemergence, there have been frequent reports of pig farms affected by LAV-LOM-derived CSFV on Jeju Island (Fig. 1), indicating the establishment of endemic CSF that aggravates socioeconomic losses to the provincial pig industry [20,21]. ...
... In fact, the unintentional vaccination of LAV-LOM in CSFV-naïve sow herds in 2014 resulted in the reemergence of CSFV in Jeju province, the largest island of South Korea, which had achieved a CSF-free status and then prohibited prophylactic vaccination in 1998 [17][18][19]. Subsequent animal studies have revealed clinical adverse effects of the used LAV-LOM in pigs [17,20]. Since its reemergence, there have been frequent reports of pig farms affected by LAV-LOM-derived CSFV on Jeju Island (Fig. 1), indicating the establishment of endemic CSF that aggravates socioeconomic losses to the provincial pig industry [20,21]. ...
... For the control and eradication of CSF on Jeju Island, the provincial government considered switching to a vaccination policy using desirable vaccines that fulfill the requirements, includingsafetyandtheDIVAconcept,suchasCSFVE2subunit vaccines. Like the LOM vaccine, the LOM-derived field strains circulating in Jeju swine populations are grouped within the genotype 1.1 clade [17,18,21]. Considering these issues, Jeju Island necessitates an effective alternative vaccine [22].Inaddition,theCSF-E2vaccinewasdemonstrated to confer effective protection against multiple genotypes 1.1, 1.2, and 2.1 of CSFV [22][23][24][25]. ...
Purpose
Accidental vaccination with a live attenuated low-virulence strain of Miyagi (LOM) vaccine led to the reemergence of classical swine fever virus (CSFV) in Jeju province, South Korea in 2014. To control the continual outbreaks of LOM-derived CSFV, the provincial government launched a provincial mass vaccination project using a CSF-E2 subunit vaccine. We conducted this study to assess the herd immunity level and outcomes of E2 vaccine-based immunization in breeding and growing herds on Jeju Island during 2020–2021.
Materials and Methods
A large-scale vaccination trial using the Bayovac CSF-E2 vaccine investigated its efficacy in breeding and growing herds under farm application conditions (10 CSFV-affected and three CSFV-naïve swine farms).
Results
The level of herd immunity in each farm was classified into three (S1–S3) and six (G1–G6) profiles in breeding and growing herds, respectively. Immunity monitoring revealed a remarkable improvement in the herd immunity status in all farms. The majority (10/13) of farms, including CSFV-free farms, showed the S1G1 immunity profile in 2021, indicating the appropriate implementation of the advised vaccination regime. Moreover, there were significant decreases in Erns seropositivity from 100% to 50% and 25.9% to 4.3% at farm and pig levels, respectively. In particular, all farms were confirmed as CSFV free in the growing-finishing herds.
Conclusion
Our large-scale trial demonstrated the effectiveness of the E2 subunit vaccine in establishing herd immunity stabilization and eliminating CSFV circulation in the affected farms and highlighted the need for a provincial vaccination policy to regain the CSF-free status on Jeju Island.
... In Korea, there were over 424 cases of FMD outbreak in over 11 epidemics from 2000 to 2019, which resulted in severe loss of more than 3 billion US dollar in the livestock industry. Among various transmission routes of livestock infectious diseases, transmission via human and vehicle movement is a major cause of the livestock infection (Büttner et al., 2013;Choe et al., 2019;Fèvre et al., 2006). Moreover, the infectious disease outbreaks were aggravated by livestock regions with high farm density owing to the vulnerability of closely located livestock farms to the rapid spread of viruses between the farms. ...
... Yet, these MLVs do not permit the differentiation between naturally infected and vaccinated animals, and are extremely sensitive to temperature changes; therefore, they require a strict cold chain of distribution, which often fails in underdeveloped countries (6). A third limitation of MLVs is the risk of reversion of the virulence of vaccine strain, an issue that has been described in several countries (7)(8)(9)(10). Due to this associated risk, the European Union prohibited the use of MLVs. ...
E2-CD154 is a subunit vaccine candidate that has been proven to be safe and to protect piglets from classical swine fever (CSF). In this study, those previous findings were confirmed and extended to a larger number of animals in a phase III clinical trial conducted on two production farms in Pinar del Río province. All animals in both farms were vaccinated with two doses of E2-CD154 on days 0 and 21. The study extended up to 60 weeks. The vaccine was well tolerated in piglets between 15 and 28 days of life, with neither local nor systemic side effects documented. Immunized pregnant sows were capable of transmitting high levels of maternally-derived neutralizing antibodies (MDNAs) to their offspring (Unit A, geometric mean titer = 1:1295, minimum value 1:100 and Unit B geometric mean titer = 1:474, minimum value 1:150), well above the protection threshold (1:50). These high MDNA titers in the piglets did not interfere with the immunogenicity of the candidate. All vaccinated piglets evaluated at random (more than 10% of 2804 vaccinated) developed protective neutralizing antibody titers higher than 1:400 at the four time points analyzed (nine, 21, 41, and 44 weeks) in both farms. The results of this study confirm the safety, immunogenicity and robustness of this vaccine candidate in this sensitive pig category in the field.
... Consequently, Jeju Province, the largest island of South Korea, declared CSFfree status and banned the CSF vaccine mandate in 1998 [9]. However, this provincial non-vaccination policy caused several CSF outbreaks on Jeju Island by the unintentional introduction or injection of the MLV-LOM into CSFV-naïve herds from the mainland of South Korea, drawing suspicion regarding the safety of this sole national commercial vaccine [8,[10][11][12]. Despite the benefits of its use for protection and prevention, the MLV-LOM carries authentic disbenefits of using the live attenuated vaccine, which includes the possibility of reversion to virulence and adverse effects in the field [13,14]. ...
Purpose:
Classical swine fever (CSF) reemerged on CSF-free Jeju Island where vaccination is not practiced by the unintentional injection of a live attenuated vaccine (modified live attenuated vaccines-low-virulence Miyagi [MLV-LOM]) in 2014. Since the Jeju provincial authority is considering adopting a voluntary immunization policy using a CSF-E2 subunit vaccine to combat LOM-derived CSF endemic, this study aimed to evaluate in Jeju herds.
Materials and methods:
Two vaccination trials using the Bayovac CSF-E2 vaccine licensed for use in South Korea assessed the safety and humoral immunity of the CSF-E2 vaccine in breeding (trial 1) and nursery animals (trial 2) under farm application conditions.
Results:
Neither local nor systemic (including reproductive) adverse effects were objectively observed in pregnant sows and young piglets following a respective vaccination regime at pregnancy or weaning, respectively. Trial 1 showed that sows immunized with the CSF-E2 vaccine possessed high and consistent E2-specific and neutralizing antibody levels. The CSF-E2 vaccine-immunized pregnant sows subsequently conferred appropriate and steady passive immunity to their offspring. In trial 2, a double immunization scheme of the CSF-E2 vaccine in piglets at 40 and 60 days of age could elicit a consistent and long-lasting adequate antibody response. Additionally, the two trials detected no Erns-specific antibody responses, indicating that CSF-E2 vaccine can differentiate infected from vaccinated animals (DIVA).
Conclusion:
Our trial data collectively provide invaluable information on applying the CSF-E2 subunit vaccine to circumvent the possible drawbacks associated with the MLV-LOM concerning the safety, efficacy, and DIVA, in the LOM-endemic field farms and contribute to advanced CSF eradication on Jeju Island.
... Owing to its CSF-free status, Jeju Province, the largest island of South Korea, where vaccination was banned in 1998, has been exempted from this mandate (Song et al., 2013). However, since the provincial novaccination policy, Jeju Island has experienced five outbreaks because of the unintentional introduction of the MLV-LOM into CSFV-naïve pigs via unexpected routes from mainland South Korea (Choe et al., 2019;Kim et al., 2008). ...
Background
Reemergent local outbreaks of classical swine fever (CSF) occurred simultaneously in multiple pig farms on CSF‐free Jeju Island, South Korea, in 2014 because of inadvertent injection of a commercial CSF (LOM) vaccine into pregnant sows. The LOM virus has since spread across the island and has become endemic in Jeju herds, raising concern about possible reversion to the virulence of the LOM vaccine. We previously isolated LOM‐derived field CSF virus (CSFV) strains with unique insertion‐deletion (INDEL) mutations in the 3′‐untranslated region (UTR), designated LOM‐derived Jeju 3′‐UTR INDEL variants, from CSF‐recurrent swine farms on Jeju Island in 2019.
Methods
The present study conducted animal experiments to investigate whether a 2019 emergent LOM 3′‐UTR INDEL variant, KNU‐1905, has reverted to a pathogenic form in conventional pigs (n = 10).
Results
Experimental animal infection showed that pigs inoculated with the commercial LOM vaccine strain developed no adverse effects compared to the sham‐infected pigs. However, KNU‐1905 displayed pathogenic characteristics in pigs, including clinical symptoms (e.g., lethargy, conjunctivitis, nasal discharge, and diarrhoea), weight loss, and gross lesions. Moreover, viremia, virus shedding in faeces and nasal fluids, and viral loads in various tissues of all the KNU‐1905‐infected pigs were highly significant, in contrast to those of the LOM‐infected group in which CSFV RNA was detected only in the serum, nasal, and tonsil samples of one identical pig.
Conclusions
Overall, the LOM‐derived field isolate with molecular variations induced clinical adverse events in pigs, which commonly shed considerable amounts of CSFV. This study provides evidence that the genetic evolution of the LOM‐derived CSFV circulating on Jeju Island might have allowed the LOM vaccine to recover its primary prototype and that these variants might have induced chronic or persistent infection in pigs that can shed CSFV in field farms leading to a risk of transmission among pigs or farms in this former CSF‐free region.
... On Jeju Island, which is located off the southernmost tip of mainland South Korea, CSF vaccination has not been implemented since 1999. However, frequent detection of CSF-antibody-positive pigs was confirmed as being due to contamination of the live attenuated CSF vaccine strain [15]. However, some CSF antibody-positive cases are thought to be due to infection by BVDV, although this has not been reported formally. ...
On Jeju Island, South Korea, pigs have not been vaccinated against classical swine fever (CSF) since 1999. Analysis of bovine viral diarrhea virus (BVDV) isolated from pigs on Jeju Island between 2009 and 2019 identified five BVDV-1a strains and one BVDV-1b strain. These BVDV types were shown to be the same types as BVDV strains isolated from neighboring cow farms. BVDV antibody-positive pigs (both BVDV-1 and -2) were also detected at 54 of 168 pig farms during this period. In pig infection experiments using BVDV-1a and -2a strains isolated from neighboring cow farms, BVDV-1a was detected in the blood of one of four pigs infected at both 6 and 35 days post-infection (dpi) and in the blood of two of the four pigs at 28 dpi. Pigs showed higher anti-BVDV-1 titers (5.5 ± 1.5 log2) at 35 dpi. BVDV-2a was detected in the blood of one of four pigs infected with this virus at 28 dpi only, and lower antibody titers (2.75 ± 0.75 log2) were seen in these pigs at 35 dpi. While BVDV infection is not particularly pathogenic in pigs, it is still important to monitor porcine BVDV infections due to a differential diagnosis of CSFV.
... In 2015, Japan was officially announced by OIE to be CSF-free and added to the list of countries with CSF-free status after conducting a successful 10-year eradication program; however, several sporadic reemerging incursions transmitted from wild boar to the domestic population have been reported recently [39][40][41]. In addition, CSF reemerged accidentally in the Jeju island of South Korea after the unintentional vaccination of live attenuated CSF vaccine (LOM strain) on naïve pigs in 2014 [42][43][44]. The alignment of whole-genome sequences of field virulent CSFV strains in the Jeju island (Jeju LOM strain) and the LOM vaccine strain revealed high identity on nucleotide (98.7-99.0%) ...
Background
Classical swine fever (CSF) is one of the most devastating pig diseases that affect the swine industry worldwide. Besides stamping out policy for eradication, immunization with vaccines of live attenuated CSF or the CSF-E2 subunit is an efficacious measure of disease control. However, after decades of efforts, it is still hard to eliminate CSF from endemically affected regions and reemerging areas. Most of previous studies demonstrated the efficacy of different CSF vaccines in laboratories under high containment conditions, which may not represent the practical performance in field farms. The inadequate vaccine efficacy induced by unrestrained factors may lead to chronic or persistent CSF infection in animals that develop a major source for virus shedding among pig populations. In this study, a vaccination-challenge-cohabitation trial on specific-pathogen-free (SPF) pigs and long-term monitoring of conventional sows and their offspring were used to evaluate the efficacy and the impact of maternally derived antibody (MDA) interference on CSF vaccines in farm applications.
Results
The trials demonstrated higher neutralizing antibody (NA) titers with no clinical symptoms and significant pathological changes in the CSF-E2 subunit vaccine immunized group after CSFV challenge. Additionally, none of the sentinel pigs were infected during cohabitation indicating that the CSF-E2 subunit vaccine could provoke adequately acquired immunity to prevent horizontal transmission. In field farm applications, sows immunized with CSF-E2 subunit vaccine revealed an average of higher and consistent antibody level with significant reduction of CSF viral RNA detection via saliva monitoring in contrast to those of live attenuated CSF vaccine immunized sows possessing diverse antibody titer distributions and higher viral loads. Furthermore, early application of the CSF-E2 subunit vaccine in 3-week-old piglets illustrated no MDA interference on primary immunization and could elicit consistent and long-lasting adequate antibody response suggesting the flexibility of CSF-E2 subunit vaccine on vaccination program determination.
Conclusions
The CSF-E2 subunit vaccine demonstrated significant efficacy and no MDA interference for immunization in both pregnant sows and piglets. These advantages provide a novel approach to avoid possible virus shedding in sow population and MDA interference in piglets for control of CSF in field farm applications.
... Expression of cytokine genes was examined in pigs inoculated with the two CSF vaccines (Flc-LOM-BE rns + SE and LOM + SE) and in the mock pigs. Peripheral blood mononuclear cells (PBMCs) were collected on different dpv and the expression of IFN-γ, IL-6, IL-10, and TNF-α mRNA was measured by qRT-PCR, as described previously [12,13] ( Table 1). Briefly, 10 mL of PBS (phosphate-buffered saline) was mixed with 10 mL of collected blood and then overlayered with 4 mL of lympho-prep. ...
... The concentration of the extracted RNA was measured in a spectrophotometer and cDNA was synthesized using a Nanohelix cDNA synthesis kit. qRT-PCR was performed by mixing 1 mL of synthesized cDNA with 500 nM of forward and reverse primers and 1 × SSO Advanced Universal Probes Supermix (Bio-Rad, Hercules, CA, USA, 172-5280) [12,13] (Table 1). The β-actin and GAPDH were used as internal controls [13] ( Table 1). ...
... qRT-PCR was performed by mixing 1 mL of synthesized cDNA with 500 nM of forward and reverse primers and 1 × SSO Advanced Universal Probes Supermix (Bio-Rad, Hercules, CA, USA, 172-5280) [12,13] (Table 1). The β-actin and GAPDH were used as internal controls [13] ( Table 1). Relative quantification (RQ) of mRNA expression was calculated by the 2 −∆∆Ct method [14]. ...
Herein, we compared the productivity of pigs inoculated with one of two classical swine fever (CSF) vaccines (low virulent of Miyagi (LOM) or Flc-LOM-BErns) plus the swine erysipelothrix rhusiopathiae (SE) vaccine. The feed intake and weight increase of the pigs inoculated with Flc-LOM-BErns + SE were normal. However, the feed intake of the pigs inoculated with LOM + SE dropped sharply from four days post-vaccination (dpv). In addition, the slaughter date was an average of eight days later than that of the pigs inoculated with Flc-LOM-BErns + SE. All pigs inoculated with the Flc-LOM-BErns + SE vaccine were completely differentiated at 14 days against CSF Erns antibody and at approximately 45 days against the bovine viral diarrhea virus (BVDV) Erns antibody; the titers were maintained until slaughter. Leucopenia occurred temporarily in the LOM + SE group, but not in the Flc-LOM-BErns + SE group. Expression of tumor necrosis factor (TNF)-α and IFN-γ was significantly (p < 0.05) higher in the LOM + SE group than in the mock (no vaccine) group. When conducting the same experiment on a breeding farm, the results were similar to those of the laboratory experiments. In conclusion, the biggest advantage of replacing the CSF LOM vaccine with the Flc-LOM-BErns vaccine is improved productivity.
... For CSFV, live attenuated vaccines have long been considered to meet all the requirements. Nevertheless, a recent outbreak that occurred in a previously CSF-free island applying live attenuated low-virulence strain of Miyagi (LOM) vaccine inoculation led to a later study showing that the employed LOM strain can cause viremia and cross the placenta to piglets [41,42]. This research reminds us of the need to recharacterize the safety of the live attenuated vaccines using more recent technologies. ...
Classical swine fever (CSF), caused by CSF virus (CSFV), is one of the most devastating viral epizootic diseases of swine in many countries. To control the disease, highly efficacious and safe live attenuated vaccines have been used for decades. However, the main drawback of these conventional vaccines is the lack of differentiability of infected from vaccinated animals (DIVA concept). Advances in biotechnology and our detailed knowledge of multiple basic science disciplines have facilitated the development of effective and safer DIVA vaccines to control CSF. To date, two types of DIVA vaccines have been developed commercially, including the subunit vaccines based on CSFV envelope glycoprotein E2 and chimeric pestivirus vaccines based on infectious cDNA clones of CSFV or bovine viral diarrhea virus (BVDV). Although inoculation of these vaccines successfully induces solid immunity against CSFV, none of them could ideally meet all demands regarding to safety, efficacy, DIVA potential, and marketability. Due to the limitations of the available choices, researchers are still striving towards the development of more advanced DIVA vaccines against CSF. This review summarizes the present status of candidate CSFV vaccines that have been developed. The strategies and approaches revealed here may also be helpful for the development of new-generation vaccines against other diseases.
... However, a CSFV lapinized vaccine C-strain against CSF globally lacks the capability of serological differentiation between infected and vaccinated animals (DIVA) [5]. Some studies have confirmed that the utilization of live-attenuated or inactivated disease-causing pathogen vaccines carries the risk of virulence instability and mortality after immunization [6,7]. Therefore, the secretion antigen E2 is an optimal candidate for the CSFV vaccine development. ...
Protein-based self-assembling nanoplatforms exhibit superior immunogenicity compared with soluble antigens. Here, we present a comprehensive vaccine strategy for displaying classical swine fever virus (CSFV) E2 glycoprotein on the surface of ferritin (fe) nanocages. An E2-specific blocking antibody assay showed that the blocking rates in pE2-fe/Gel02 (84.3%) and a half-dose cohort of E2-fe/Gel02 (81.9%) were significantly higher (p < 0.05) than that in a ferritin-free cohort of pE2/Gel02 (62.7%) at 21 days post immunization (dpi) in vivo. Furthermore, quantitation of neutralizing potency revealed that a highly significant difference (p < 0.001) was observed between the pE2-fe/Gel02 cohort (1:32, equivalent to live-attenuated strain C at 1:32) and the pE2/Gel02 cohort (1:4) at 21 dpi. Moreover, the innate immune cytokines of IL-4 and IFN-γ activated by the half-dose (20 μg) cohort of E2-fe/Gel02 were equivalent to those elicited by the full dose (40 μg) of purified E2 in the pE2/Gel02 cohort at most time points. In conclusion, we successfully obtained an antigen-displaying E2-ferritin nanoplatform and confirmed high ferritin-assisted humoral and cellular immunities. Our results provided a novel paradigm of self-assembling nanovaccine development for the defense and elimination of potentially pandemic infectious viral pathogens.
