Hand, foot, and mouth disease (HFMD) is a highly contagious disease with no specific treatment. Since it is common in immunocompromised children under the age of 5, there is a need to develop a safe vaccine. Virus-like particles (VLPs) are similar structures to viruses with the lack of genetic material which makes them impossible to replicate and infect, and therefore have a high level of biological safety and are considered to have high value as vaccines. In this study, the insect virus expression system that is widely used for vaccine and drug production due to its high post-translational modification efficiency, was used to produce VLPs for Coxsackievirus type A6 and A10, which are recently reported to be the main causes of HFMD. For this purpose, the selection of promoters that can control the timing and intensity of expression of 3CD protein, which is essential for VLPs assembly but has been reported to be cytotoxic, was conducted to construct an optimal expression form for HFMD-VLP.

Foot-and-mouth disease (FMD), which affects cloven-hoofed animals, is economically important because of its highly contagious nature. FMD virus (FMDV), the causative agent of FMD, involves seven serotypes (O, A, Asia1, C, and SAT 1-3). Serotype Asia1 is unique to the Asian territory and is subdivided into nine genetic groups (G-I-IX) based on nucleotide variations in the VP1 sequence. Asia1 Shamir, the most representative Asia1 vaccine, is not highly protective against the Asia1/MOG/05 (G-V) lineage found in North Korea in 2007. Therefore, we investigated whether a chimeric virus strain (Asia1/MOG/Shamir), in which the VP4, VP2, and VP3 sequences of Asia1/MOG/05 were combined with the VP1 sequence of Asia1 Shamir, can simultaneously protect against both viruses. We determined the optimal viral growth conditions for the commercial utilization of this chimeric virus strain. Of the three types of cell culture media, the Cellvento medium resulted in the highest amount of antigen in the samples. The chimeric strain was proliferated in a small bioreactor to produce a test vaccine, and its immunogenicity was evaluated in pigs. The virus neutralization (VN) titer against the Asia1 Shamir virus was > 1/100 after the second immunization with the chimeric vaccine in pigs. In addition, a single dose of the test vaccine resulted in a VN titer of > 1/100 against the Asia1/MOG/05 strain. Taken together, our chimeric vaccine strain provided sufficient protection against the Asia1/MOG/05 and Asia1 Shamir viruses, suggesting its potential as a novel vaccine for both these strains.

The Republic of Korea has implemented an obligatory vaccination on major livestock breeds to prevent and eradicate nationwide foot and mouth disease (FMD) since the end of 2010. The government has executed massive serological survey to check the immune level of various herds after vaccination, and seropositive rates against FMD virus (FMDV) structural proteins can be measured to assess FMD immunity level. The purpose of this study is to investigate the FMDV serological level of every cattle breeding farm in the country and to determine whether there is a significant difference between groups classified by time, age, and management authority. A total of 5,781 serum samples was collected in 18 cattle breeding farms from 2020 to 2021, and the seropositive rates were measured using PrioCHECK FMDV Type O ELISA kit. Firstly, the cattle breeding farms were classified by which they are managed: the central government, the local government, and the private agency. Every management authority had a seropositive rate of 99.5% or higher. Secondly, the samples were divided into 6 to 12 months old, 12 to 24 months old, and 24 months or more. The 6 to 12 months old group in 2020 showed a significantly low seropositive rate of 98.1%, but it was improved by implementing the enhanced vaccination policy from 2021 to 100%. In summary, there are considerably high seropositive rates including all groups with time, age, and by which they are managed, which means the FMD vaccination in cattle breeding farms is well-managed.

Foot-and-mouth disease (FMD) is a very deadly and highly contagious disease that occurs in various cloven-hoofed animals. Korea imports vaccines including non-vaccinated serotype for the vaccine bank. The two company vaccines imported from 2019 to 2021 were evaluated through multiple tests based on national standard assay. SN titers for the vaccine of company A were more than 1.5 log10, those of company B vaccine in the geometric mean were at least 1.72. All imported vaccines exceeded the evaluation criteria, and the potency of each vaccine was above its own company standard. Stockpiled vaccines for emergency may help to control non-vaccinated serotypes of FMD outbreak nationally.

This study evaluated the effect of a combination of acetaminophen (AAP), vitamin C (VC) and thioctic acid (TA) on reducing serum cortisol concentrations in mice with foot-and-mouth disease (FMD) vaccination. For 5 days from 3 days before FMD vaccination to 2 days after vaccination, mice were orally administered with AAP 600 mg/kg feed (n=25, AAPT), combination of AAP 600 mg and VC 200 mg per kg feed (n=25, AVCT) and combination of AAP 600 mg, VC 200 mg and TA 20 mg per kg feed (n=25, AVTT), respectively. From day 1 to day 7 after FMD vaccination, the cortisol concentration of all groups treated with the drug was significantly decreased compared to that of the positive control group with FMD vaccination (p<0.05). In conclusion, the combined treatment of AAP, VC and TA was the most effective in relieving stress from FMD vaccination compared to the single treatment.

Foot-and-mouth disease (FMD) is a highly contagious vesicular disease that affects cloven-hoofed animals, causing substantial economic losses to the livestock industry. The causative FMD virus (FMDV) comprises four structural proteins (VP1, VP2, VP3, and VP4) and several non-structural proteins. Among the capsid proteins, VP4 is the most conserved, making it an attractive target as a diagnostic and vaccine antigen, regardless of FMDV serotype. In this study, we attempted to express the VP4 protein N-terminally fused to a glutathione S-transferase (GST) tag in Escherichia coli. Whereas VP0 and VP2 proteins were expressed in the soluble fraction, we failed to detect VP4, even in the insoluble fraction. To investigate the effect of VP4 C-terminal amino acid residues on protein expression, we constructed three VP4 mutants fused to GST, among which the mutant in which the C-terminal 15 amino acid residues had been deleted showed the highest level of protein expression. Furthermore, protein expression was observed even in the mutant in which three amino acid residues (DKK) had been fused to the C terminus. However, unlike the other two mutants, the wild-type VP4 mutant was poorly expressed, thereby indicating that the C-terminal amino acid residues could play a pivotal role in determining expression of the VP4 protein in E. coli.

This study evaluated whether fevernill, which is primarily composed of acetaminophen, vitamin C, and anhydrous citric acid, is effective in relieving stress caused by foot-and-mouth disease virus (FMDV) vaccination in calves. Three-month-old calves from a farm in Korea were randomly assigned to one of three groups (n = 10 per group: control [untreated], group A [FMDV vaccination], and group B [FMDV vaccination + addition of fevernill 0.2% to feed for five days after vaccination]). Body weights, antibody formation, clinical symptoms, serum parameters were measured in the 14 days following vaccination. Total weight gain and average daily gain during the experiment period were group A (12.00±1.15 kg, 0.86±0.08 kg/day) compared to group B (13.57±0.98 kg, 0.97±0.07 kg/day) was significantly improved (p<0.05). There was no significant difference in the formation of antibodies against the FMDV vaccine between group A and group B, though the antibody value of group B tended to be higher than that of group A. The pre-inflammatory cytokine TNF-α value was 74.47±19.26 pg/ml in group A and 59.05±11.88 pg/ml in group B on the 5th day of the experiment, which was significantly lower in group B than in group A (p<0.05). Also, cortisol concentrations were significantly lower in group B than in group A (p<0.05). In conclusion, the feeding of fevernil is judged to be helpful in mitigating the side effects caused by FMD vaccination, and thus it is thought to be able to prevent the decrease in productivity caused by vaccination.

This study compared the immune responses, stress relief and weight gains of needle or needle-free intramuscular and needle-free intradermal vaccination in pigs. When the same amount of a foot-and-mouth disease (FMD) vaccine was administered to pigs, antibody titers at 4 weeks after the 1st and 2nd FMD vaccination were not significantly different between the needle (IM-S) and needle-free (NM-P250) intramuscularly vaccinated groups, but the weight gain of NM-P250 was significantly increased compared to that of IM-S at 8 weeks after the 2nd FMD vaccination (p<0.05). In addition, serum cortisol concentrations of NM-P250 were considerably decreased compared to those of IM-S on the 5th and 7th day after the 1st and 2nd FMD vaccination (p<0.05). However, the antibody titers of IM-S vaccinated with 2 mL of FMD vaccine were significantly increased compared to those of the needle-free intradermal vaccinated group with 0.5 mL of FMD vaccine at 4 weeks after the 1st and 2nd FMD vaccination (p<0.05). In conclusion, the needle-free intramuscular injection for the FMD vaccination can be chosen for weight gain and stress relief in pigs.

We conducted diagnostic investigations to analyze the causes of abortions (46 cases, 65.7%), deaths (22 cases, 31.4%) and muscular lesions (2 cases, 2.9%) occurred after foot and mouth disease (FMD) vaccination in livestock farms in Korea. Bacterial culture, enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) were performed to detect the causative agents of abortion in bovine and caprine. The diagnostic results showed that 36 (51.4%) cases, referring as “Identified”, were occurred by influence of underlying disease including bovine viral diarrhea (12 cases, 17.1%), neosporosis (7 cases, 10.0%), septicemic colibacillosis (5 cases, 7.1%), Q fever (4 cases, 5.7%) and other abnormal conditions (8 cases, 11.4%) not by vaccination. Other 2 (3.0%) cases were suspected to be vaccine-associated adverse reaction on the basis of pathological findings (shock lung, oil-component-induced granuloma) and clinical symptoms (dyspnea with pulmonary edema). The other 32 (45.7%) cases were determined “Unknown” because any pathogens and pathological changes were not identified. However, many of the “Unknown” cases were presumptive to be the vaccine-related adverse reaction based on epidemiological investigation, especially, the cases which showed the clinical signs within 2 days after the vaccination. It is important to conduct pathological, microbilogical and epidemiological investigation to diagnose whether the cases are from vaccine-associated adverse reaction or not.

The abnormal meat could caused by abscess, fibrosis and granuloma in the region of the neck by the adverse effect of foot-and-mouth disease (FMD) vaccination practice for Korean swine. After FMD vaccination was implemented in 2010, the number of incidences of abnormal meat has been increasing. In this study, it was evaluated whether needless intradermal injection (NII) of FMD vaccine reduces abnormal meat at the injection site in comparison to conventional intramuscular injection (IM). In addition, the onset of humoral immunity was analyzed in order to see if NII of this vaccine is able to mount comparable antibody response with IM. This study was carried out in four Korean pig farms. The O-type FMD vaccine was implemented via NII at three farms and the control group was vaccinated via IM. Antibody titers were compared from the serum samples taken from 10 random pigs at age of 8, 12, 16 and 22~24 weeks of age. The O+A type FMD vaccine was also compared with the same protocol. When test animals were slaughtered, incidence, type and size of abnormal meat were recorded. The results of this study showed that the antibody titers between intradermal and intramuscular group were similar but a significant difference in the incidence of abnormal meat formation was observed between two groups (p < 0.05). In summary, needless intradermal injection of FMD vaccination was proven to be effective for the onset of humoral immunity and reducing abnormal meat formation.

This study examined the spatial autocorrelation of the 2016 foot and mouth disease (FMD) outbreaks in South Chungcheong to determine the association between the disease epidemics and pig farm vehicle movements. Two spatial autocorrelation testing methods were used: Moran’s I and Getis-Ord G statistics. The Moran’s I statistic for the FMD outbreak areas was -0.239, and its p-value was less than 0.007. The median Getis-Ord G statistic for the FMD outbreak areas was -0.323. The results indicated that the geographical distribution of the FMD outbreak areas was not spatially homogeneous. The spatial autocorrelation of the 2016 FMD epidemics was considered by applying a geographical weighted Poisson regression (GWPR) model in the analysis, in which pig farm vehicle movements were used as risk factors for the 2016 FMD epidemics. The number of FMD-infected farms per second-level administrative province (si or gun) was used as a dependent variable. The number of farm vehicle movements within the province (within variable), from one province to other provinces (outbound variable), or from other provinces to one province (inbound variable), were included as independent variables in the GWPR model. The results of the GWPR model were as follows. The estimated median coefficient of the log-transformed within variable, the log-transformed outbound variable, and log-transformed inbound variable were -0.000, 0.010, and -0.009, respectively. The optimal bandwidth for the GWPR model was 80.49, and the AIC score was 89.35. The results showed that the GWPR model would provide an understanding of the relationship between the 2016 FMD epidemics and pig farm vehicle movements

In the case of foot-and-mouth disease (FMD), there is a great deal of impact on the national economy due to the disposal of diseases, the cost of disease control such as vaccination, reduction of productivity, and restriction of international trade of livestock products. Therefore, appropriate diagnostic methods for sensitive, accurate and rapid identification of virus serotypes are continuously required in terms of early prevention of FMD. This study was conducted to confirm the feasibility of immuno-PCR diagnostic method for the more sensitive detection of Korean FMD virus (FMDV). We synthesized a partial FMD type A viral gene. Protein antigen, monoclonal and polyclonal antibodies of FMDV were cloned, expressed and purified and then magnetic particles were attached to polyclonal antibodies and and oligomers to monoclonal antibodies for the immnuno-PCR. We confirmed the antigen-antibody and oligomer reaction using ELISA, Western blot, and real-time PCR. These results show that Korean FMDV can be detected by using difference of Ct values between positive group and negative group using immuno-PCR.. The results of this study also suggest that this technique will be the basis of the diagnosis method to detect Korean FMDV more sensitively in the future.

The cost-effectiveness of foot-and-mouth disease (FMD) control strategies was evaluated using a simulation model fitted to the 2010/11 FMD epidemic in the city of Andong, Republic of Korea. Seven FMD-control strategies were evaluated with respect to the direct cost of a FMD-control strategy, such as slaughtering, movement restriction, and vaccination. All the strategies included pre-emptive slaughtering, movement restriction, and vaccination, but the levels of each control option were different. The simulated median cost of the baseline FMD-control strategy (three kilometers of pre-emptive slaughtering area, 100 days of movement restriction and vaccination of all FMD-susceptible animals in the study area) was estimated to be USD 99.7 million. When a five kilometer vaccination area was applied (with the other control measures being the same as the baseline strategy), the simulated median cost was reduced to USD 81.1 million from USD 99.7. The simulated median costs were USD 107.6 million for a five kilometer radius slaughtering area and USD 168.8 million for 60 days of movement restriction. The FMD-control strategy cost decreased with increasing number of farms depopulated per day. The probability of passive surveillance being effective or the probability of the successful implementation of movement restrictions were increased. Cost-effectiveness analysis is a suitable tool for evaluating the financial consequences of FMD-control strategies by comparing the cost of control strategies for a specific area.

A simulation model of the 2010/11 foot-and-mouth disease (FMD) epidemic in the city of Andong, Republic of Korea was constructed to evaluate the epidemiologic effectiveness of FMD-control strategies. Seven FMD-control strategies were evaluated with respect to a number of epidemiologic indicators relating to the outbreak, including the number of infected animals, number of infected farms, and epidemic duration. The FMD-control strategies in the model consisted of pre-emptive slaughtering, movement restriction, and vaccination; however, levels of each control option differed. The constructed model was not perfectly representative of the 2010/11 FMD epidemic, although it was considered to mimic the actual FMD epidemic in its prediction of two outcomes: the median number of simulated FMD-detected farms was 294 (range 207–515), which was close to the number of farms detected (299) during the actual FMD epidemic (x2=87.239, df=98, p = 0.774); and the simulated epidemic curve was visually similar to the actual epidemic curve of the 2010/11 FMD epidemic. The effectiveness evaluation of simulated FMD-control strategies emphasized the amount the FMD outbreak size could have increased if the radius of the pre-emptive slaughtering area or the duration of movement restriction were decreased.

This study evaluated the effect of reduced glutathione (GSH) for the reduction of stress and inflammatory response in calves inoculated with foot-and-mouth disease (FMD) vaccine. Twenty-five calves were divided into five groups of 5 calves. The negative control (NC) did not receive any vaccination or drug treatment. The positive control (PC), GSH-25, GSH-50 and GSH-100 were intramuscularly injected with GSH at concentrations of 0, 25, 50 and 100 mg / 10 kg body weight (BW), respectively, for 3 days after FMD vaccination. On day 3, 5 and 7 post-treatment, the serum cortisol and tumor necrosis factor- α (TNF-α) levels in GSH-50 and GSH-100 were significantly decreased compared with those in PC (p < 0.05). However, there was no significant difference in the serum cortisol and TNF-α levels between GSH-100 and NC 3 and 5 days post-treatment, and between GSH-50, GSH-100, and NC 7 days post-treatment. The results from this study suggest that treatment of 50 mg / 10 kg BW GSH for 3 days is useful for the reduction of stress and inflammatory response caused by FMD vaccination in calves.

구제역은 발생 시 전염이 쉽게 일어나며 심각한 경제적 피해를 일으키는 질병이다. 구제역의 방역정책은 발견 직 후 빠른 살처분이 최선책이나, 전파 속도나 상황 등에 따 라 타지역 백신 접종 등의 방법을 시행할 수도 있다. 이러 한 방법을 적용하기 위해서는 구제역을 빠르고 정확하게 진단할 필요성이 있다. 개발된 진단법들은 구제역의 확진, 혈청형의 동정, 백신 접종 후 항체의 생성 확인 등에 사용 된다. 많은 진단법들이 개발되었지만 아직은 빠른 시간 내 에 검출이 가능하며 동시에 정확성도 가진 방법이 드물다. 그렇기에 기존의 방법들을 개선시킨 새로운 진단법이 필 요하다. 현재는 대부분 혈청학적 진단법인 ELISA에 의존 하거나 분자 유전학적 기술인 PCR을 사용한다. 가장 최근 기술은 그 둘을 합치는 방법으로, 어떻게 하면 더 신속하 고 저비용이면서, 민감하고 정확한 방법이 될 수 있을지 연구가 진행되고 있다.

This study investigated the changes in appetite and behavior of cattle and pigs after foot-and-mouth disease (FMD) vaccination. This study involved ten calves and ten pigs, each divided into two groups of five animals. One group of each animal was vaccinated with an FMD vaccine (FMD-V), and the other group was used as a non-treated control (CON). Each animal’s appetite and behavior were observed before vaccination and for seven days post-vaccination. In the FMD-V groups, appetite and behavior scores during the seven days post-vaccination were significantly decreased compared to those in the CON groups. The only exception was the seventh day post-vaccination in the swine behavior scores.

Seven outbreaks of foot-and-mouth disease (FMD) have occurred in South Korea during the period January 2000-September 2015. The Korean government changed national goal to FMD-free country with vaccination after the November 2010 outbreak when approximately 3.5 million cattle and pigs were culled. With regard to vaccination, Korean pig producers have claimed that the occurrence of injection site reaction (inflammatory or non-inflammatory granuloma) is potentially associated with intensive vaccination campaign since 2011. The present study was undertaken to assess the incidence of injection site lesions in slaughtered pigs caused by FMD vaccination and the corresponding economic losses. Data obtained from two meat packers were classified into 3 vaccination periods: non-vaccination (July-November, 2010, n=96,959); one injection (July-November, 2014, n=162,089); and two injections (March-July, 2015, n=161,928). A total of 420,976 carcasses from 6,526 farms were analyzed. The incidence of the lesions was 18.6% for non-vaccination, 46.5% for one injection, and 73.7% for two injections. Economic loss per head slaughtered due to removal of the lesions was estimated to 1,302 won (US$ 1.1) for non-vaccination, 8,286 won (US$ 7.2) for one injection, and 17,378 won (US$ 15.1) for two injections (converted using 2015 exchange rate where Korean won 1,150 = 1 US$). It was estimated that the national annual losses excluding costs of an FMD vaccine and its application is US$ 115 million for one injection and US$ 241 million for two injections. The adoption of measures that cause minimal tissue damages and economic losses would appear to be of high priority.

A cell line of bovine origin was immortalized to isolate foot-and-mouth disease virus (FMDV). The immortalization was performed by infection of bovine primary epithelial cells with a recombinant retrovirus that overexpressed the human telomerase (hTERT), after primary culture of fetal bovine kidney tissue and removal of fibroblasts. After cloning the immor- talized cell line into single cells, the cloned cell lines were named JNUBK-1, JNUBK-2, JNUBK-3 and JNUBK-4, according to their characteristics. To confirm the epithelial phenotype of the cell lines JNUBK-3 and JNUBK-4, which showed stable proliferation capability over 35 generations after immortalization, the expression of cytokeratin and fibronectin was measured. Finally, the FMDV titer in the JNUBK-3 and JNUBK-4 cell lines was measured and was 800∼2,000 times higher than that of the currently used cell line IRBS-2. In conclusion, more sensitive isolation and production of FMDV became possible through the use of the immortalized JNUBK-3 and JNUBK-4 cell lines.