• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.350-358
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• 2023

Hand-foot-and-mouth disease (HFMD) is a viral infectious disease that occurs in children under 5 years of age. Its main causes are coxsackievirus (CV) and enterovirus (EV). Since there are no efficient therapeutics for HFMD, vaccines are effective in preventing the disease. To develop broad coverage against CV and EV, the development of a bivalent vaccine form is needed. The Mongolian gerbil is an efficient and suitable animal model of EV71 C4a and CVA16 infection used to investigate vaccine efficacy following direct immunization. In this study, Mongolian gerbils were immunized with a bivalent inactivated EV71 C4a and inactivated CVA16 vaccine to test their effectiveness against viral infection. Bivalent vaccine immunization resulted in increased Ag-specific IgG antibody production; specifically, EV71 C4a-specific IgG was increased with medium and high doses and CVA16-specific IgG was increased with all doses of immunization. When gene expression of T cell-biased cytokines was analysed, Th1, Th2, and Th17 responses were found to be highly activated in the high-dose immunization group. Moreover, bivalent vaccine immunization mitigated paralytic signs and increased the survival rate following lethal viral challenges. When the viral RNA content was determined from various organs, all three doses of bivalent vaccine immunization were found to significantly decrease viral amplification. Upon histologic examination, EV71 C4a and CVA16 induced tissue damage to the heart and muscle. However, bivalent vaccine immunization alleviated this in a dose-dependent manner. These results suggest that the bivalent inactivated EV71 C4a/CVA16 vaccine could be a safe and effective candidate HFMD vaccine.

• Korean Journal of Veterinary Service
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• v.41 no.1
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• pp.9-13
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• 2018

The best way to prevent foot-and-mouth disease (FMD) constantly occurring in Korea will be vaccination. In this study, FMD vaccines were given to Korean native cattle (Hanwoo), dairy cattle, and pigs to investigate the antibody positive rate of FMD vaccine by age in year and month. Hanwoo, dairy cattle, and pigs showed antibody positive rates of 99.5%, 97.7%, and 95.9%, respectively. High antibody positive rates more than 95% were found in Hanwoo and dairy cattle. In particular, high antibody positive rates were found in Hanwoo and dairy cattle regardless of age. Pigs showed a relatively low antibody positive rate of 57.6% at 3 months of age and then constantly maintained a high antibody positive rate of above 95.0% after 4 months of age. As a result of this study, high antibody positive rates were found when regular FMD vaccination was given to newborn calves and piglets after FMD vaccination twice to them. Therefore, it is considered the most important to receive vaccination thoroughly according to vaccination plan in order to prevent FMD.

• Clinical and Experimental Pediatrics
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• v.58 no.3
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• pp.112-115
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• 2015

Hand, foot, and mouth disease (HFMD) is an acute, mostly self-limiting infection. Patients usually recover without any sequelae. However, a few cases are life threatening, especially those caused by enterovirus 71 (EV71). A 12-month-old boy was admitted to a primary hospital with high fever and vesicular lesions of the mouth, hands, and feet. After 3 days, he experienced 3 seizure episodes and was referred to our hospital. On admission, he was conscious and his chest radiograph was normal. However, 6 hours later, he suddenly lost consciousness and had developed a massive pulmonary hemorrhage that continued until his death. He experienced several more intermittent seizures, and diffuse infiltration of both lung fields was observed on chest radiography. Intravenous immunoglobulin, dexamethasone, cefotaxime, leukocyte-depleted red blood cells, fresh frozen plasma, inotropics, vitamin K, and endotracheal epinephrine were administered. The patient died 9 hours after intubation, within 3 days from fever onset. EV71 subgenotype C4a was isolated retrospectively from serum and nasopharyngeal swab by real-time reverse transcription-polymerase chain reaction. Here, we report a fatal case of EV71-associated HFMD with sudden-onset massive pulmonary hemorrhage and suspected encephalitis.

• IMMUNE NETWORK
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• v.9 no.6
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• pp.265-273
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• 2009

Foot-and-mouth disease virus (FMDV) is a small single-stranded RNA virus which belongs to the family Picornaviridae, genus Apthovirus. It is a principal cause of FMD which is highly contagious in livestock. In a wild type virus infection, infected animals usually elicit antibodies against structural and non-structural protein of FMDV. A structural protein, VP1, is involved in neutralization of virus particle, and has both B and T cell epitopes. A RNA-dependent RNA polymerase, 3D, is highly conserved among other serotypes and strongly immunogenic, therefore, we selected VP1 and 3D as vaccine targets. VP1 and 3D genes were codon-optimized to enhance protein expression level and cloned into mammalian expression vector. To produce recombinant protein, VP1 and 3D genes were also cloned into pET vector. The VP1 and 3D DNA or proteins were co-immunized into 5 weeks old BALB/C mice. Antigen-specific serum antibody (Ab) responses were detected by Ab ELISA. Cellular immune response against VP1 and 3D was confirmed by ELISpot assay. The results showed that all DNA- and protein-immunized groups induced cellular immune responses, suggesting that both DNA and recombinant protein vaccine administration efficiently induced Ag-specific humoral and cellular immune responses.

• Biomolecules & Therapeutics
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• v.22 no.1
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• pp.41-46
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• 2014

Enterovirus 71 (EV71) is the predominant cause of hand, foot and mouth disease (HFMD). The antiviral activity of hederasaponin B from Hedera helix against EV71 subgenotypes C3 and C4a was evaluated in vero cells. In the current study, the antiviral activity of hederasaponin B against EV71 C3 and C4a was determined by cytopathic effect (CPE) reduction method and western blot assay. Our results demonstrated that hederasaponin B and 30% ethanol extract of Hedera helix containing hederasaponin B showed significant antiviral activity against EV71 subgenotypes C3 and C4a by reducing the formation of a visible CPE. Hederasaponin B also inhibited the viral VP2 protein expression, suggesting the inhibition of viral capsid protein synthesis.These results suggest that hederasaponin B and Hedera helix extract containing hederasaponin B can be novel drug candidates with broad-spectrum antiviral activity against various subgenotypes of EV71.

• Korean Journal of Veterinary Research
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• v.49 no.3
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• pp.221-229
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• 2009

Foot-and-mouth disease (FMD) is the most contagious disease of mammals. The use of inactivated vaccine can be chosen to prevent or control FMD. However, vaccination against one serotype of FMDV doses not cross-protect against other serotypes and may not protect fully against some strains of the same serotype. Appropriate selection of vaccine strain is an important element in the control of FMD. The immunity of vaccine antigens should be matched against newly circulating viruses. The phylogenetic analysis of serotype Asia1 reported from China, Mongolia, North Korea and Russia since 2005 shows that they are all classified into genetic group V, but the strain, Asia1/Shamir (ISR/89) which have been used as a vaccine strain in Korea, is clustered into different genetic group. So, in this study the serological relationship between the isolate (Asia1/MOG/05; MOG) and the Shamir strain was determined by ELISA and virus neutralization test. Even though the matching value of the virus (MOG) against the vaccinated sera in target animals was not so high, the vaccinated animals elicited antibodies enough for protection after vaccinated once or twice. Conclusively, we suggest that the vaccine containing Asia1/Shamir antigen could protect the genetic group V strains circulating in East Asia currently if vaccinated twice or the more.

• Food Science of Animal Resources
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• v.38 no.3
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• pp.498-505
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• 2018

This study was aimed to investigate the effects of the type O foot-and-mouse disease vaccine (FMDV) on the incidence of abnormal meat such as granuloma or abscess formation at the injection site in pork and its associated economic losses. At 56 d of age, piglets were inoculated with FMDV by one of three administration routes: N-Neck (a conventional needle-syringe injection into the neck), N-Ham (a conventional needle-syringe injection into the ham), and Non-Neck (injection with a needle-free device into the neck). The injection sites were visually examined for the presence of a granuloma or abscess, and the incidence rate of abnormal meat was calculated. The gross weight of the portion of the pork carcasses condemned because of granuloma or abscess formation was measured and multiplied by the weekly sales price to calculate the total economic losses. After implementation of FMDV, the economic losses were approximately six times higher than before implementation. Granuloma or abscess formation was significantly higher in the N-Neck and Non-Neck groups, in which the vaccine was inoculated into the neck area, than in the N-Ham group (N-Neck and N-Ham vs Non-Neck, p<0.05). These results suggest that the incidence of lesions could be reduced if the ham route was used for vaccination.

• Korean Journal of Veterinary Service
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• v.36 no.1
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• pp.15-21
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• 2013

Three serotypes (O+A+Asia1 type) of the foot-and-mouth disease (FMD) vaccine were injected into cloven-hoofed animals in Korea after the nationwide spread of FMD at the end of 2010. This study was conducted to investigate FMD antibody development after FMD vaccination, and to determine whether there was a significant correlation between the antibody titer of the sow and the antibody titer of the growing pigs. The antibody titer (percentage inhibition [PI] titer) of the sow (gilt) after FMD vaccination was maintained at a level higher than 50 (P<0.05) for 5 months. A higher PI titer for the 1-month-old growing pigs corresponded with greater inhibition of the PI titer of the vaccinated growing pigs (P<0.05). A negative correlation (P<0.05) between the PI titer of the 1-month-old growing pigs and the PI titer of 3-month-old growing pigs, 4-month-old growing pigs after FMD vaccination at 2 months, 3months was identified, with a coefficient of determination ($R^2$) of 0.274. Thus the PI titer of the growing pigs was inhibited to a greater degree when vaccination was performed at 2 months of age than at 3 months. However, many other factors likely influence growing pigs' PI titer in addition to the PI titer of the sow and age at vaccination, given that the coefficient of determination was somewhat lower.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.6
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• pp.792-799
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• 2019

Objective: This study was conducted to evaluate whether the co-injection of antioxidants together with foot-and-mouth disease (FMD) vaccination has the potential to attenuate the negative effects caused by vaccination in Holstein finishing steers. Methods: A total of 36 finishing Holstein steers (body weight [BW]: $608{\pm}45.6kg$, 17 months old) were randomly allocated to one of three treatments: i) control (CON, only FMD vaccination without any co-injection), ii) co-injection of commercial non-steroidal anti-inflammatory drugs (NSAID) with FMD vaccination at a ratio of 10:1 (NSAID vol/FMD vaccine vol) as a positive control (PCON), iii) co-injection of commercial mixture of vitamin E and selenium with FMD vaccination (VITESEL) (1 mL of FMD vaccine+1 mL of antioxidants per 90 kg of BW). Changes in growth performance and blood parameters because of treatments were determined. Results: No significant difference in BW, average daily gain, and dry matter intake of the steers was observed among the treatments. The FMD vaccination significantly increased white blood cells (WBC), neutrophils, platelets, and mean platelet volume (p<0.01) in blood analysis. The count of lymphocyte tended to increase after vaccination (p = 0.08). In blood analysis, steers in VITESEL tended to have higher numbers of WBC, neutrophils, and platelets compared to that of other treatments (p = 0.09, 0.06, and 0.09, respectively). Eosinophils in VITESEL were higher than those in PCON (p<0.01). Among blood metabolites, blood urea nitrogen and aspartate transaminase were significantly increased, but cholesterol, alanine transferase, inorganic phosphorus, Mg, and albumin were decreased after FMD vaccination (p<0.01). Conclusion: The use of antioxidants in FMD vaccination did not attenuate growth disturbance because of FMD vaccination. The metabolic changes induced by vaccination were not controlled by the administration of antioxidants. The protective function of antioxidants was effective mainly on the cell counts of leukocytes.

• Journal of Veterinary Science
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• v.24 no.1
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• pp.15.1-15.13
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• 2023

Background: Inactivated vaccines are limited in preventing foot-and-mouth disease (FMD) due to safety problems. Recombinant virus-like particles (VLPs) are an excellent candidate for a novel vaccine for preventing FMD, given that VLPs have similar immunogenicity as natural viruses and are replication- and infection-incompetent. Objectives: The 3C protease and P1 polyprotein of type O FMD virus (FDMV) was expressed in yeast Hansenula polymorpha to generate self-resembling VLPs, and the potential of recombinant VLPs as an FMD vaccine was evaluated. Methods: BALB/c mice were immunized with recombinant purified VLPs using CpG oligodeoxynucleotide and aluminum hydroxide gel as an adjuvant. Cytokines and lymphocytes from serum and spleen were analyzed by enzyme-linked immunosorbent assay, enzyme-linked immunospot assay, and flow cytometry. Results: The VLPs of FMD were purified successfully from yeast protein with a diameter of approximately 25 nm. The immunization of mice showed that animals produced high levels of FMDV antibodies and a higher level of antibodies for a longer time. In addition, higher levels of interferon-γ and CD4⁺ T cells were observed in mice immunized with VLPs. Conclusions: The expression of VLPs of FMD in H. polymorpha provides a novel strategy for the generation of the FMDV vaccine.